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Background Performance validity tests (PVTs) and symptom validity tests (SVTs) are essential to neuropsychological evaluations, helping ensure findings reflect true abilities or concerns. It is unclear how PVTs and SVTs perform in children who received radiotherapy for brain tumors. Accordingly, we investigated the rate of noncredible performance on validity indicators as well as associations with fatigue and lower intellectual functioning. Methods Embedded PVTs and SVTs were investigated in 98 patients with pediatric craniopharyngioma undergoing proton radiotherapy (PRT). The contribution of fatigue, sleepiness, and lower intellectual functioning to embedded PVT performance was examined. Further, we investigated PVTs and SVTs in relation to cognitive performance at pre-PRT baseline and change over time. Results SVTs on parent measures were not an area of concern. PVTs identified 0–31% of the cohort as demonstrating possible noncredible performance at baseline, with stable findings 1 year following PRT. Reliable digit span (RDS) noted the highest PVT failure rate; RDS has been criticized for false positives in pediatric populations, especially children with neurological impairment. Objective sleepiness was strongly associated with PVT failure, stressing need to consider arousal level when interpreting cognitive performance in children with craniopharyngioma. Lower intellectual functioning also needs to be considered when interpreting task engagement indices as it was strongly associated with PVT failure. Conclusions Embedded PVTs should be used with caution in pediatric craniopharyngioma patients who have received PRT. Future research should investigate different cut-off scores and validity indicator combinations to best differentiate noncredible performance due to task engagement versus variable arousal and/or lower intellectual functioning. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy enables the delivery of a high radiation dose to tumors while sparing surrounding normal tissues. Inaccurate patient positioning may lead to underdosing of the targeted tumor and overdosing of nearby healthy tissues. Before a course of proton therapy, a CT scan is acquired for treatment planning with the patient in the treatment position, and this image dataset is used as a reference for patient localization at each treatment fraction. Radiation therapists perform daily cone-beam CT (CBCT) image guidance to align the patient to closely match the planning CT and minimize inaccuracies in radiation delivery. In this study, CBCT scans were systematically collected with clinical and treatment information to investigate questions related to image guidance, setup uncertainty, and patient motion during the treatment of pediatric brain tumors. Knowledge gained from this study provides a basis for designing safe and optimal proton treatments. This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion. Orthogonal radiographs were acquired consecutively with CBCT for paired comparisons of 40 patients. Translational and rotational errors were converted from 6 degrees of freedom to a scalar by a statistical approach that considers the distance from the target to the isocenter. The 95th percentile of setup uncertainty was reduced by daily CBCT from 10 mm (manual positioning) to 1–1.5 mm (after correction) and increased to 2 mm by the end of fractional treatment. A larger variation existed between the roll corrections reported by radiographs vs. CBCT than for pitch and yaw, while there was no statistically significant difference in translational variation. A quantile mixed regression model showed that the 95th percentile of intrafractional motion was 0.40 mm lower for anesthetized patients ( p = 0.0016 ). Considering additional uncertainty in radiation-imaging isocentricity, the commonly used total plan robustness of 3 mm against positional uncertainty would be appropriate for our study cohort. [ABSTRACT FROM AUTHOR]

Purpose : Accurate detection of leptomeningeal metastasis (LM) is critical for risk stratification and treatment of pediatric brain tumors. Poor-quality staging MRI has been associated with decreased survival in this population, but technical factors differentiating good from poor quality screening MRIs remain undefined. To test the hypothesis that key technical factors are associated with accurate MRI diagnosis of leptomeningeal metastasis in children with leptomeningeal seeding brain tumors. Methods: MRIs acquired at outside facilities and repeated in our institution within 35 days for 75 children with leptomeningeal seeding tumors were assessed for slice thickness and gap; use of T2 FLAIR + Contrast, acquisition plane of 3DT1WI + Contrast (brain); axial T1 + Contrast sequence, and use of pre-contrast T1 images (spine). Reported findings were recorded as positive, negative, or equivocal for LM and classified as true positive (TP; unequivocal metastasis), false negative (FN; not reported), false positive (FP; resolved without treatment), or true negative. Wilcoxon signed-rank and Fisher's exact test were used to assess technical differences between TP and FN MRIs. Results: Rate of LM detection was greater with smaller interslice gap in brain (P = 0.003) and spine (P = 0.002); use of T2 FLAIR + Contrast (P = 0.005) and sagittal plane for 3DT1WI + Contrast (P = 0.028) in brain; and use of alternatives to axial TSE/FSE in spine (P = 0.048). Slice thickness was not significant. Pre-contrast T1WI did not contribute to LM diagnosis in spine. Conclusion: Using post-contrast T2 FLAIR and sagittal 3DT1 in brain, small/no interslice gap, and avoiding TSE/FSE axials in spine may facilitate leptomeningeal metastasis detection in children with brain tumors. [ABSTRACT FROM AUTHOR]

Purpose: To generate synthetic relative proton stopping power (sRPSP) images from magnetic resonance imaging (MRI) sequence(s) and develop an online quality assurance (QA) tool for sRPSP to facilitate safe integration of magnetic resonance (MR)‐only proton planning into clinical practice. Materials and methods: Planning computed tomography (CT) and MR images of 195 pediatric brain tumor patients were utilized (training: 150, testing: 45). Seventeen consistent‐cycle generative adversarial network (ccGAN) models were trained separately using paired CT‐converted RPSP and MRI datasets to transform a subject's MRI into sRPSP. T1‐weighted (T1W), T2‐weighted (T2W), and FLAIR MRI were permutated to form 17 combinations, with or without preprocessing, for determining the optimal training sequence(s). For evaluation, sRPSP images were converted to synthetic CT (sCT) and compared to the real CT in terms of mean absolute error (MAE) in Hounsfield units (HU). For QA, sCT was deformed and compared to a reference template built from training dataset to produce a flag map, highlighting pixels that deviate by >100 HU and fall outside the mean ± standard deviation reference intensity. The gamma intensity analysis (10%/3 mm) of the deformed sCT against the QA template on the intensity difference was investigated as a surrogate of sCT accuracy. Results: The sRPSP images generated from a single T1W or T2W sequence outperformed that generated from multi‐MRI sequences in terms of MAE (all p < 0.05). Preprocessing with N4 bias and histogram matching reduced MAE of T2W MRI‐based sCT (54 ± 21 HU vs. 42 ± 13 HU, p = 0.002). The gamma intensity analysis of sCT against the QA template was highly correlated with the MAE of sCT against the real CT in the testing cohort (r = ‐0.89 for T1W sCT; r = ‐0.93 for T2W sCT). Conclusion: Accurate sRPSP images can be generated from T1W/T2W MRI for proton planning. A QA tool highlights regions of inaccuracy, flagging problematic cases unsuitable for clinical use. [ABSTRACT FROM AUTHOR]

Purpose: Medulloblastoma is one of the most common malignant brain tumors in children. To date, the treatment of average-risk (non-metastatic, completely resected) medulloblastoma includes craniospinal radiation therapy and adjuvant chemotherapy. Modern treatment modalities and now risk stratification of subgroups have extended the survival of these patients, exposing the long-term morbidities associated with radiation therapy. Prior to advances in molecular subgrouping, we sought to reduce the late effects of radiation in patients with average-risk medulloblastoma. Methods: We performed a single-arm, multi-institution study, reducing the dose of craniospinal irradiation by 25% to 18 Gray (Gy) with the goal of maintaining the therapeutic efficacy as described in CCG 9892 with maintenance chemotherapy. Results: Twenty-eight (28) patients aged 3-30 years were enrolled across three institutions between April 2001 and December 2010. Median age at enrollment was 9 years with a median follow-up time of 11.7 years. The 3-year relapse-free (RFS) and overall survival (OS) were 79% (95% confidence interval [CI] 58% to 90%) and 93% (95% CI 74% to 98%), respectively. The 5-year RFS and OS were 71% (95% CI 50% to 85%) and 86% (95% CI 66% to 94%), respectively. Toxicities were similar to those seen in other studies; there were no grade 5 toxicities. Conclusions: Given the known neurocognitive adverse effects associated with cranial radiation therapy, studies to evaluate the feasibility of dose reduction are needed. In this study, we demonstrate that select patients with average-risk medulloblastoma may benefit from a reduced craniospinal radiation dose of 18 Gy without impacting relapse-free or overall survival. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00031590 [ABSTRACT FROM AUTHOR]

Purpose: Vasculopathy (VAS) is a significant complication associated with radiation therapy in patients treated for brain tumors. We studied the type, location, severity, timing, and resolution of VAS in children with craniopharyngioma treated with proton radiation therapy (PRT) and evaluated predictors of stenosis (STN) using a novel patient and imaging-based modeling approach.Methods and Materials: Children with craniopharyngioma (n = 94) were treated with 54 Gy relative biological effectiveness PRT in a clinical trial, NCT01419067. We evaluated VAS type, location, severity, and resolution. VAS events were segmented and related to their location, operative corridor, PRT dose, and vascular territory to facilitate mixed effect logistic regression modeling of spatial predictors of STN events.Results: Forty-five (47.9%) patients had 111 instances of confirmed VAS (pre-PRT n = 37, 33.3%). The median time to post-PRT VAS was 3.41 years (95% confidence interval, 1.86-6.11). STN events were observed post-PRT in 23.4% (n = 22) of patients. Post-PRT VAS was detected by cerebral angiogram in 9.6% (n = 9), severe in 4.3% (n = 4), and compensated on perfusion in 2.1% (n = 2). Revascularization was required for 5 (5.3%) patients. Postsurgical, pre-PRT VAS, and PRT dose to unperturbed vessels were predictive of STN. The effect of PRT on STN was negligible within the surgical corridor.Conclusions: VAS often precedes PRT and was the strongest predictor of post-PRT STN. The adverse effect of PRT on STN was only apparent in unperturbed vasculature beyond the operative corridor. [ABSTRACT FROM AUTHOR]