LaRiviere, Michael J.

ABSTRACT Background Radiotherapy is a cornerstone of treatment for pediatric central nervous system (CNS) tumors, but dose selection remains uniform despite interpatient variability in tumor radiosensitivity. This is consequential in children, for whom toxicity can have lifelong effects. Genomic-adjusted radiation dose (GARD) integrates tumor genomics with delivered radiation dose to quantify the biological effect of radiotherapy and has been validated across adult malignancies. Its relevance in pediatric CNS tumors is unknown. Methods We performed a cohort study using gene expression and data from 246 pediatric patients with high-grade glioma, medulloblastoma, or ependymoma from the Children’s Brain Tumor Network. GARD was calculated using a sequencing-adapted radiosensitivity index integrated with radiation dose through the linear–quadratic model. Associations of GARD and physical radiation dose with event-free and overall survival were evaluated using Cox proportional hazards models stratified by tumor type and anatomic location. Patients who did not receive radiotherapy comprised a negative control cohort (sham-GARD). Results Among patients receiving radiotherapy, physical dose was uniform, whereas GARD showed substantial interpatient variability in biological effect. Higher GARD was associated with improved event-free survival (hazard ratio [HR] 0·90, 95% CI 0·83–0·97; p=0·004) and overall survival (HR 0·90, 95% CI 0·83–0·99; p=0·018). Physical dose was not associated with either endpoint. Among patients who did not receive radiotherapy, sham-GARD was not associated with outcomes, supporting GARD as a treatment-specific predictor rather than a prognostic biomarker. Conclusions In pediatric CNS tumors, the biological effect of radiotherapy quantified by GARD was associated with outcomes, whereas physical dose was not. These findings challenge uniform radiotherapy dosing and support genomically informed dose individualization. Prospective evaluation of GARD-guided radiotherapy is warranted to optimize tumor control while minimizing long-term toxicity in children.

ABSTRACTBackgroundWe investigated mental health diagnoses (MHDs) in mycosis fungoides (MF) patients compared to the general population, evaluated risk factors, and studied survival outcomes in a large population database.MethodsMF patients from the Utah Cancer Registry diagnosed from 2001 to 2014 were matched with up to five general population individuals from the Utah Population Database. MHDs were retrospectively tracked in both populations (median follow‐up = 6.67 years). Risk factors for new MHDs among MF patients were studied using the Cox proportional hazards model. Overall survival (OS) and disease‐specific survival (DSS) were assessed using Kaplan–Meier analysis.ResultsThe incidence of anxiety disorders (HR = 1.99, 95% CI [1.16, 3.42]) and delirium/dementia disorders (HR = 2.43, 95% CI [1.05, 5.63]) was higher among MF patients than the matched general population. Among MF patients, Charlson Comorbidity Index (CCI) ≥ 2 and BMI < 18 kg/m2 were risk factors for new anxiety disorders. Radiation therapy, CCI ≥ 2, and female gender were risk factors for new delirium/dementia disorders. The 15‐year OS was worse for MF patients with versus without an MHD (36% vs. 81%, HR 2.62, 95%CI [1.24, 5.65]). The 15‐year DSS also worsened for MF patients with versus without an MHD (63% vs. 97%, HR 6.55, 95%CI [1.64, 26.2]).ConclusionsMF patients developed anxiety and delirium/dementia disorders at rates above the general population, and MHDs correlated with worse DSS and OS. Careful mental health monitoring may be an actionable step towards improving health‐related quality of life in this population.