Citations

The treatment landscape of invasive early-stage and metastatic breast cancer is evolving constantly. These NCCN Guidelines Insights focus on recent updates included in the most recent version (version 5.2025) of the NCCN Guidelines for Breast Cancer specific to workup, locoregional therapy, surveillance, and systemic neoadjuvant/adjuvant therapy recommendations for invasive, nonmetastatic breast cancer.

Abstract Context Pharmacological options for the treatment of early severe childhood obesity are limited. Objective This retrospective case series evaluates the effect of topiramate on weight and cardiometabolic parameters in young children with severe obesity, including those with hypothalamic etiologies. Methods This is a retrospective case series including 14 children with severe obesity, who were treated with topiramate prior to age 12 years. Anthropometric and metabolic data were analyzed. Results The median age at initiation of topiramate treatment was 10.1 years (range, 7.9-11.2 years) and 64% were boys. At baseline, the median body mass index (BMI) was 149% of the 95th percentile (range, 136%-200%). The median treatment duration was 14 months (interquartile range, 9.5-24 months), with a maximum tolerated dose of 75 mg (range, 50-150 mg). There was a median decrease in BMI% of the 95th percentile of 8% (95% CI, −15 to −1.02; P = .042), and a reduction in BMI z score by 0.37 (95% CI, −0.66 to −0.05; P = .028). The most notable response was in a child with hypothalamic obesity who experienced a 35-point reduction in BMI% of the 95th percentile over 24 months. While 11 of 14 children showed reduction in BMI, 3 had no change or increase in their BMI. No significant changes were observed in cardiometabolic markers or linear growth. Conclusion Topiramate monotherapy resulted in significant BMI reductions in young children with severe obesity, including those with hypothalamic obesity. Further prospective randomized controlled trials are warranted to assess its long-term efficacy for obesity management in young children.

Abstract Background Adolescent and young adult (AYA) patients remain underrepresented in neuro-oncology research. Despite being the second most common primary brain tumor in this population, meningiomas have not been studied using age-specific molecular analyses. DNA methylation-based classification and prognostic tools have transformed meningioma care. This study aimed to evaluate the performance of these tools across age groups. Methods We analyzed 1,568 meningiomas with DNA methylation and clinical data, including 18 pediatric patients (<15 years), 195 AYA patients (15-39 years), and 1,355 adult patients (>39 years). Pediatric and AYA (P/AYA) tumors were combined and compared with adult tumors. The performance of established molecular classifiers and recurrence predictors, as well as differences in chromosomal copy number alterations were compared across age groups. Results While histologic grading was comparable between cohorts, P/AYA tumors displayed significantly fewer aggressive molecular groups and lower frequencies of chromosomal arm losses, including 1p, 6q, and 14q. The adult-trained recurrence predictor failed in the P/AYA population (AUC 0.57), despite similar score distributions. Retraining the model on an age-specific cohort using an identical analytic framework improved performance (AUC 0.79) and enabled effective stratification of progression-free survival (P = 0.00054). Importantly, 1p loss retained prognostic significance within the P/AYA group, supporting its clinical utility. Conclusions Molecular tools developed in adult-dominant cohorts do not generalize to younger patients due to both biological divergence and exclusion from model development. These findings underscore the need for age-specific molecular frameworks and highlight the imperative of including P/AYA populations in precision neuro-oncology research to ensure lifespan-equitable care.