The BraTS-PEDs dataset provides the largest, multi-institutional, publicly available collection of annotated multiparametric MRI scans of pediatric high-grade gliomas, enabling standardized benchmarking and development of AI tools in pediatric neuro-oncology.

10031 Background: Studies have shown the clinical benefits of D and T, in combination and as monotherapy, to treat adult and pediatric patients with BRAF V600 mutation-positive cancers. Here, we report the interim results from a long-term, follow-up study for patients from previously completed clinical trials that assessed the use of D and/or T in pediatric patients with MAPK pathway-activated tumors. Methods: This ongoing, global, open-label, multi-center study evaluated the long-term effects (general health, growth and development) of D and/or T in pediatric patients with tumors with MAPK pathway activation from previous studies that assessed (1) safety, tolerability and pharmacokinetics of D in solid tumors (NCT01677741); (2) pharmacodynamics and clinical activity of T or D+T in cancer or plexiform neurofibromas (NCT02124772); and (3) safety and efficacy of D+T in glioma (NCT02684058). The patients in this study followed the same treatment as at the end of the parent study. The duration of this study is 7 years after the first patient first visit (FPFV) (November 2019). The primary objective is to assess the long-term safety of the treatment. Results: Of a total 165 patients, 157 received the study treatment (D [n=28], T [n=21], D+T [n=108]) and 8 patients were for observation only. Most patients with low-grade glioma (LGG) and high-grade glioma (HGG) had BRAF V600 mutation (n=129). The median duration of exposure was approximately 21 months. From FPFV to the data cut-off (October 2024), most of the patients (94.3%) experienced at least one adverse event (AE) with 28% patients experiencing serious AEs. The most common AE was pyrexia (36.9%). AEs leading to treatment discontinuation occurred in 3.8% of total patients (D [3.6%], T [9.5%], D+T [2.8%]). One on-treatment death was reported in the D+T arm due to convulsion (not related to the study treatment). No clinically meaningful changes were observed in hematological or biochemical parameters in the D+T arm. Grade ≥ 3 abnormalities were infrequent and were reported in <2% of patients, except creatine kinase increase (5.7%). Assessment of vital signs, growth, electrocardiography, bone age and Tanner staging did not reveal any new safety signals. In the D+T arm, as per investigator assessment, overall response (complete + partial) was 27.7% for patients with BRAF V600E mutation positive LGG (stable disease: 63.9% patients) and 41.2% for patients with BRAF V600E mutation positive HGG. The median progression-free survival and median overall survival were not reached. Conclusions: In this long-term study, reported AEs were in line with established safety profile of D and/or T. Except more than normal increase in weight, no significant impact of D and/or T was observed on growth, sexual maturation and skeletal development. The benefit-risk remained favorable toward D and/or T therapy in pediatric patients with MAPK pathway-activated tumors. Clinical trial information: NCT03975829 .

BACKGROUND:Astroblastomas are rare brain tumors predominantly affecting children and young adults, for which molecular subtypes and clinical management remain undefined. METHODS:We analyzed tumor samples, molecular profiles, and clinical data from 200 patients, classified as "Astroblastoma, MN1-altered" under WHO criteria, using DNA methylation profiling, DNA/RNA profiling/sequencing, and survival analyses. RESULTS:DNA methylation analyses identified 3 groups: Group A (n = 143, characterized by MN1::BEND2 fusions, predominantly supratentorial location, with striking female predominance and favorable survival); Group B (n = 37, epigenetically and transcriptionally closely related to Group A, but characterized by EWSR1::BEND2 fusions, with spinal and infratentorial locations and poor prognosis); and Group C (n = 20, epigenetically and transcriptionally distinct, characterized by MN1::CXXC5 fusions, exclusively supratentorially located, with favorable survival). Progression-free and overall survival were significantly shorter in Group B (5-year PFS 14%; 10-year OS 54%) compared to A (5-year PFS 47%; 10-year OS 89%) and C (5-year PFS 75%; 10-year OS 89%). Radiotherapy improved PFS in Group B (hazard ratio 0.25), while no clear benefit was identified for Groups A and C. CONCLUSIONS:Astroblastoma, MN1-altered, comprises 3 molecularly and clinically distinct groups, characterized by different fusion genes, including those without MN1. These new insights, including the identification of potential predictive biomarkers like 14q/16q loss, provide a framework for the development of risk-stratified therapeutic approaches. Importantly, we identified a molecularly defined high-risk group that benefits from radiation therapy. Our findings redefine Astroblastoma as a molecularly diverse tumor type, propose a refined classification, support the development of risk-adapted therapeutic strategies and provide a rational standard of care.

Glioblastoma multiforme (GBM) is the most aggressive primary brain malignancy with limited treatment options and poor clinical outcomes. There is growing interest in using Zika virus as a treatment for GBM due to its selectivity in finding and killing rapidly proliferating neural cells. Several studies reproducibly show that Zika can effectively kill GBM cells. We sought to uncover the molecular mechanisms driving this cytotoxic effect by performing a meta-analysis of transcriptomic studies in which Zika virus was used to kill GBM cells. We integrated four datasets from studies on GBM and added neuroblastoma (NBM) studies as an outgroup comparator. Our analysis identified a shared molecular signature of the Zika-infected GBM cell. Interestingly, GBM cells killed by the Zika virus showed dysregulation of pathways commonly implicated in proliferation and metastasis, including TNF, NF-κB, and p53 signaling. Using a hypothesis-free design, we found several long non-coding RNAs (lncRNAs) that were consistently dysregulated in Zika-infected GBMs, many of which have previously unrecognized roles in cancer cell death. Among this group, we validated four lncRNAs for a role in Zika-mediated oncolysis. We functionally tested MELTF-AS1, TIPARP-AS1, NR2F1-AS1, and SLC9A3-AS1 in adult GBM cell lines using siRNA-mediated knockdown. Silencing of MELTF-AS1 augmented Zika-induced cell death, while knockdown of TIPARP-AS1, NR2F1-AS1, and SLC9A3-AS1 attenuated oncolysis, identifying lncRNAs whose modulation is associated with altered Zika-mediated cytotoxicity. These findings elucidate candidate mechanisms of Zika oncolysis in GBM cell lines, highlight novel lncRNA targets, and support further exploration of lncRNA modulation as a strategy to enhance oncolytic virotherapy for GBM and related malignancies.

Glioblastoma multiforme (GBM) is the most aggressive primary brain malignancy with limited treatment options and poor clinical outcomes. There is growing interest in using Zika virus as a treatment for GBM due to its selectivity in finding and killing rapidly proliferating neural cells. Several studies reproducibly show that Zika can effectively kill GBM cells. We sought to uncover the molecular mechanisms driving this cytotoxic effect by performing a meta-analysis of transcriptomic studies in which Zika virus was used to kill GBM cells. We integrated four datasets from studies on GBM and added neuroblastoma (NBM) studies as an outgroup comparator. Our analysis identified a shared molecular signature of the Zika-infected GBM cell. Interestingly, GBM cells killed by the Zika virus showed dysregulation of pathways commonly implicated in proliferation and metastasis, including TNF, NF-κB, and p53 signaling. Using a hypothesis-free design, we found several long non-coding RNAs (lncRNAs) that were consistently dysregulated in Zika-infected GBMs, many of which have previously unrecognized roles in cancer cell death. Among this group, we validated four lncRNAs for a role in Zika-mediated oncolysis. Experimental testing of MELTF-AS1, TIPARP-AS1, NR2F1-AS1, and SLC9A3-AS1 in adult GBM cell lines confirmed pronounced differential gene expression. Silencing of MELTF-AS1 augmented Zika-induced cell death, while knockdown of TIPARP-AS1, NR2F1-AS1, and SLC9A3-AS1 attenuated oncolysis, identifying a novel class of pro-oncolytic lncRNAs that critically contribute to ZIKV-mediated cytotoxicity. These findings elucidate Zika’s oncolytic mechanisms, highlight novel lncRNA targets, and support further exploration of lncRNA modulation as a strategy to enhance oncolytic virotherapy for GBM and related malignancies.

Abstract Background Fibroblast growth factor receptor (FGFR) alterations define an actionable subset of pediatric low-grade gliomas (pLGG), but real-world data describing clinicoradiographic phenotypes, molecular diversity, and treatment outcomes remain limited. Methods We performed a bi-institutional retrospective review of pediatric patients with FGFR-altered pLGG evaluated at Children’s National Hospital and the Dmitry Rogachev National Research Center between 2014 and 2024. Clinical features, histopathology, imaging characteristics, extent of resection, systemic therapies (including targeted agents), radiotherapy, and outcomes were extracted through March 2025. Results Nineteen patients (mean age, 8.5 years; range, 1-18) were identified. Tumors were predominantly supratentorial (74%); 21% involved the brainstem. Imaging commonly showed T2 hyperintensity and facilitated diffusion; contrast enhancement was frequent, with serpiginous enhancement in a subset. Intratumoral hemorrhage occurred in five cases, all with FGFR1 alterations. FGFR fusions were most common (53%), followed by point mutations (26%) and internal tandem duplications (16%); all four brainstem tumors harbored FGFR1–TACC1 fusions. Surgery was the primary initial treatment (84%), but gross-total resection was achieved in 25% and was associated with durable control. Seven patients received carboplatin/vincristine, with progression in 86%. Targeted therapies (MEK inhibitors and the FGFR inhibitor erdafitinib) were used in select cases and were associated with radiographic stability in several patients, though resistance/recurrence occurred. One FGFR1 alteration was identified via CSF cell-free DNA. Conclusions FGFR alteration type was associated with distinct radiographic phenotypes and clinical patterns, supporting a potentially clinically useful genotype–phenotype framework. Responses to targeted therapy varied, highlighting the need for prospective studies to define optimal treatment sequencing, duration, and biomarker-guided management.

Abstract Background Optic pathway gliomas associated with neurofibromatosis type 1 (NF1-OPG) affect the anterior visual pathway (AVP), including the optic nerves, chiasm, and tracts. To enhance clinical applicability and accessibility of AVP morphology on MRI, we introduce CAVS-NF1 (Central AI-enabled Volumetric Service for NF1), a free, AI-powered, web tool for automated segmentation and volumetric analysis of the AVP from brain MRIs. CAVS-NF1 allows longitudinal analysis from multiple MRIs from the same patient. Methods We developed an automated pipeline utilizing a vision transformer-based AI segmentation model based on SwinUNETR. The model was trained on T1-weighted MRIs of 135 children with NF1-OPG from Children’s National Hospital (n = 60 from GE scanners) and Children’s Hospital of Philadelphia (n = 75 from Siemens scanners). Expert delineations of AVP were used for training. Post-segmentation, a template-based registration was employed to isolate the nerves and chiasm. For longitudinal analysis, we aligned the temporal volumes to compute relative changes in substructure volumes. The CAVS-NF1 framework does not require local installation and is accessible via a secure, HIPAA-compliant web interface. Results The AVP segmentation method achieved a volumetric overlap (Dice score) of 79.1 ± 8.2 %, outperforming the inter-observer variability in manual annotations (Dice: 75.6±6.2 %). The average runtime for a single analysis was 98 ± 3 seconds. In the longitudinal analysis workflow, volume change computations for AVP, nerves, and chiasm were successfully demonstrated with consistent alignment and robust segmentation performance. The CAVS-NF1 web platform is free, HIPAA-compliant, and available at https://nf1.hope4kids.io. Conclusion CAVS-NF1 enables fast, automated, and accurate longitudinal volumetric analysis of the AVP in NF1-OPG patients. The platform supports longitudinal analysis with side-by-side comparison of local changes in tumor volume over time. This AI-driven web tool enhances OPG monitoring with the potential of assessing response to therapy and is accessible to clinicians and researchers without requiring advanced technical infrastructure.

Central nervous system (CNS) tumors are the deadliest cancers in children, highlighting the need for new therapies. The tumor-associated antigens (TAAs) WT1, PRAME and survivin are widely expressed by these tumors, and a manufacturing technique has been developed to target these intracellular TAAs using autologous, nongenetically engineered T cells. Here we therefore conducted ReMIND, an open-label, phase 1 adaptive dose-finding study to determine the safety/feasibility of autologous, systemically administered trivalent T cells targeting WT1, PRAME and survivin in children with CNS tumors. Eligible patients had newly diagnosed diffuse intrinsic pontine glioma without lymphodepletion (arm A, n = 16 enrolled, n = 11 infused) and relapsed/recurrent nonbrainstem CNS malignancies without (arm B, n = 28 enrolled, n = 18 infused) or with (arm C, n = 7 enrolled, n = 4 infused) lymphodepletion. Primary end points were safety, feasibility and maximum tolerated dose determination; secondary end points included preliminary efficacy and immunobiological correlates, including in vivo TAA-T persistence and systemic immune activation. Dose level 3 (8 × 107 cells per m2 per dose) was determined as the maximum tolerated dose. Treatment was well tolerated with fatigue and headache being the most common adverse events, although two possibly related serious adverse events of tumor swelling occurred. One grade 5 event in a patient with diffuse intrinsic pontine glioma with hydrocephalus, tumor edema and respiratory failure was categorized as a dose-limiting toxicity. Median overall survival for arm A was 13.7 months from diagnosis (range, 6.2-32.0) and median progression-free survival for arms B/C was 5.0 months from infusion (range, 0.5-51.6). Three patients in arms B/C are alive without disease at 31.8, 41.2 and 51.6 months without further treatment, including one complete response. This trial met safety/feasibility primary end points with some preliminary signals of efficacy. ClinicalTrials.gov registration: NCT03652545 .

The clinical trial landscape of molecularly targeted treatments for pediatric low-grade glioma (pLGG) has created an exciting and hopeful era for both patients and clinicians alike. Despite numerous clinical trials investigating the use of targeted agents for pLGG, only two oral precision-based regimens for pLGG have received federal agency approval. However, enthusiasm surrounding recently completed early phase clinical trials has resulted in increased off-label prescribing practices beyond the federally-approved indications, despite a lack of phase 3 clinical trial data and an incomplete understanding of the long-term radiographic, functional outcomes, and toxicity for both approved and experimental therapies. These gaps in knowledge are critically important to consider when selecting therapies for patients with pLGG, as the prevention and reduction of late effects in pLGG survivors is crucial to prevent long-term morbidity. In this editorial by the clinical working group of the International pLGG Coalition, we discuss the landscape of molecularly targeted therapies for pLGG, outline the unanswered questions for the use of novel therapies in the management of pLGG, review the risks and benefits of early off-label use of targeted agents, and discuss the importance of patience and evidence-based clinical practice in the rapidly evolving era of precision medicine.

BACKGROUND:The identification of clinical and molecular heterogeneity in medulloblastoma has produced risk-stratified therapy, but establishing the most effective yet least toxic regimens has remained elusive owing to numerous treatment options. To improve risk-stratification, we performed an integrated analysis from three clinical trials. METHODS:Medulloblastoma patients from ACNS0331/NCT00085735, ACNS0332/NCT00392327, and SJMB03/NCT00085202 were included if they had methylation profiling. Molecular groups [WNT, SHH, Group 3 (G3), and Group 4 (G4)], subgroups, and copy number variations were procured from methylation profiles and mutations from next-generation sequencing. Data was assembled into an interactive portal to capture patient characteristics. Cross-trial comparisons, univariable, and multivariable analyses were conducted and used to derive a risk-stratification schema. RESULTS:Eight hundred ninety-eight patients (WNT = 131, SHH = 151, G3 = 220, G4 = 396) were included. Progression-free-survival (PFS) distributions among analogous cross-trial cohorts were not different, demonstrating no survival advantage of any one therapy over another. The addition of carboplatin to high-dose craniospinal irradiation (HDCSI) containing regimen was selectively superior in PFS in G3/G4 subgroup 3 (P = 0.048) and G3/G4 subgroup 2 (P = 0.035) to HDCSI regimens without carboplatin. Nine actionable risk-stratified groups were identified consisting of 2 WNT groups (low, high-risk), 3 SHH groups (low-, average-, very-high-risk), and 4 G3/G4 groups (low-, average-, high-, and very-high-risk). CONCLUSIONS:Our integrated cross-trial analysis suggests toxicity can be reduced by eliminating disproportionate differences in therapy in favor of a more uniform treatment backbone. Moreover, we propose and model a risk-classification system that identifies the most appropriate cohorts on which to trial significant dose reductions in craniospinal irradiation or select treatment intensifications.

Medulloblastoma is the most common malignant brain tumor in children and occurs rarely in adult patients. Treatment has evolved over the last decades to include surgery, radiotherapy to the tumor site and craniospinal axis and chemotherapy in most patients. Although various treatment approaches have been attempted, cisplatin/cyclophosphamide based approaches are the most widely used resulting in 5-year overall survival rates of 85% in standard risk patients and 50%–65% in patients with high risk disease. Late relapses do occur, although only in the minority of patients, and secondary malignancies including brain tumors, are a major complication 5 years or greater from diagnosis. Long-term sequelae from therapy are significant and novel approaches are still greatly needed. Over the last decade there have been tremendous advances in our understanding of the biology of these tumors, and they have been subdivided into four molecular groups, WNT, SHH, group 3 and group 4. Clinical trials that incorporate these subgroups into risk stratification prospectively will be important in further modifying therapy for patients in order to improve outcomes.

Abstract Pediatric brain cancers have the highest mortality rate among childhood cancers, with high-grade gliomas being particularly challenging to treat due to the blood-brain barrier and systemic toxicity. PDX rodent models require approximately six months to develop, limiting their utility for drug testing, given the median survival of 8–11 months for DIPG patients. This study highlights the advantages of zebrafish for drug toxicity assessment, pediatric brain cancer model development, and drug screening. We assessed toxicity of eight clinically relevant drugs with diverse mechanisms of action. In addition to the survival assay (LC50), we analyzed teratogenic characteristics to demonstrate the detrimental developmental toxicity, which was critical in determining drug safety for future human usage.To develop rapid and reproducible orthotopically xenografted pediatric brain cancer models, we injected approximately 80-100 mCherry expressing JHH-NF1-PA1, Res186 and TM-31 cells into the midbrain of 2 days post-fertilization zebrafish embryos and imaged daily for next 4 days to monitor the survival, progression, and invasion of the injected cells. We found that all the cell types engrafted successfully and multiplied within the developing zebrafish brain. As compared to JHH-NF1-PA1 cells, which mostly migrated caudally within the developing spinal cord, TM-31 cells migrated in multiple directions and metastasized five times more rapidly as compared to JHH-NF1-PA1 and Res186 cells. To test the efficacy of VAL-083 and AZD-1775 in high-grade gliomas, zebrafish embryos injected with mCherry-expressing SF8628 cells were treated with these drugs individually and in combination. After 72 hours, tumor invasion and migration were analyzed. The combination therapy significantly reduced tumor burden, as indicated by lower fluorescence intensity, reduced migration area, and fewer metastatic cells (p < 0.001) compared to single or no treatment. Our findings demonstrate zebrafish as a valuable, rapid, and cost-effective in vivo model for studying pediatric brain cancer, tumor metastasis, and drug screening.

Background:Infant-type hemispheric gliomas (IHG) represent a novel entity, first codified in the WHO CNS 5 classification. Due to their rarity, as well as their neuroimaging and histopathologic heterogeneity, definitive diagnosis can be challenging. In the majority of cases, the tumors are large, and difficult to fully resect. The efficacy of standard cytotoxic chemotherapy remains unclear. IHGs frequently contain receptor tyrosine-kinase (RTK) gene fusions, denoting a potential vulnerability to targeted therapy by small-molecule RTK inhibitors. Methods:We report 15 patients with IHG receiving treatment during a 5-year period. Integrated diagnosis was achieved combining histopathology, DNA methylation profiling and RNA sequencing. Ten out of 15 patients received chemotherapy. Targeted therapy with entrectinib or lorlatinib was prescribed in 5 patients after progression and in 1 as first-line treatment. Results:The median follow-up was 1.5 years (range, 0.1-5.1 years). Six patients were asymptomatic despite large volumes and diagnosed during routine ultrasound screening. Neuroimaging revealed 2 general radiographic presentation, either cystic-solid or purely solid masses. These radiologic subtypes were not associated with differences in histology or clinical behavior, but demonstrated differential gene expression profiles. Standard cytotoxic chemotherapy was administered in 10 patients, in 6 of them disease progression was observed (all with residual tumor). RTK gene fusions were revealed in all cases. Six patients were treated with targeted therapies. All patients had an initial tumor response; following which 2 had disease progression. One-year event-free survival for the entire cohort was 47% (CI 27%-80%), 2-year overall survival was 61% (CI 39%-95%). Conclusions:IHGs are comprised of 2 radiologically and molecularly distinct groups. Huge cystic tumors are frequently associated with life-threating complications. The limited efficacy of the standard cytotoxic chemotherapy and presence of kinase fusion in nearly all cases render patients with IHG candidates for targeted therapies.

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is the leading cause of mortality amongst pediatric neuro-oncologic diseases. Sonodynamic therapy with MR-guided focused ultrasound (MRgFUS) is being investigated in multiple clinical trials. METHODS: Twelve patients with DIPG were treated from August 2022-April 2024 as part of a dose-escalation protocol with SDT in a multicenter Phase 1/2 clinical trial (NCT05123534). MRgFUS was combined with the prodrug SONALA-001 (5-ALA iv) to activate its metabolite, protoporphyrin IX, and thereby induce apoptosis within tumor cells. Treatment is delivered every 4 weeks for up to 12 treatments. RESULTS: Patient ages ranged from 3-23 years and 60% were male. Twelve patients underwent a total of 45 SDT treatments (range: 2-9). When enrolled, median tumor volume was 1,337 cm3 (range: 310-2078 cm3) and duration since diagnosis was 5 months. SONALA-001 doses tested were 5 mg/kg and 10 mg/kg. Delivered ultrasonic acoustic energy ranged from 190-444 joules/cm3. After 6 months of median follow-up (range: 2-18), 2 partial responses occurred, and 9 of 12 patients had stable or improved baseline symptoms (Lansky Status), including improved mobility and diplopia. One adverse clinical event included a small non-operative epidural hematoma secondary to a stereotactic frame pin. There have been no grade 3 or worse treatment-related adverse events or dose-limiting toxicities. Ten patients are alive a median of 11 months after diagnosis; 2 have deceased; 4 have discontinued treatment. Maximum percent tumor volume changes throughout treatment ranged from a -68% reduction to over 100% enlargement. CONCLUSIONS: Preliminary analysis of twelve pediatric patients treated with SDT for DIPG demonstrates acceptable safety outcomes and promising clinical results. Additional patient enrollment and longer follow-up times are required to determine efficacy.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition associated with cutaneous and neoplastic manifestations and other physical manifestations, as well as cognitive, psychosocial, and behavioural difficulties. NF1 negatively impacts the health-related quality of life (HRQoL) of children. There is limited evidence regarding the determinants of HRQoL of children with NF1. The aim of this study was to (i) compare the HRQoL of children with NF1 and cognitive impairments to published data of healthy children and children with cancer and (ii) identify specific determinants of child and parent-proxy reports of psychosocial HRQoL. Children with NF1 and cognitive impairments (n = 135, 8–15 years 11 months) and their parents completed standardized measures assessing children’s HRQoL, behavioral and emotional functioning. Children completed a brief intelligence test. Correlations and multiple linear regressions were conducted to identify determinants of psychosocial HRQoL. Children with NF1 had significantly poorer HRQoL for all domains than published data of healthy children and significantly poorer HRQoL for Psychosocial Health, School and Social Functioning than published data of children with cancer. For child self-report, attention problems and increased social stress predicted their psychosocial HRQoL. For parent-proxy reports, activities of daily living and depression were significant predictors of children’s psychosocial HRQoL. Social stress and depression were the strongest predictors of Psychosocial HRQoL. Routine screening and early identification of depressive symptoms and interventions that promote social support, coping and resiliency may improve the HRQoL of children with NF1.

Limited labeled data could compromise the robustness of segmentation models trained on medical images. In medical imaging, manual segmentation is time-consuming and financially costly since expert human labor (radiologist etc.) is required. Active learning (AL) is a promising approach to reduce the amount of labeled data required to train a model by iteratively selecting only the most beneficial instances to be labeled from the pool of unlabeled data. Towards this, we propose a novel AL query paradigm designed for the segmentation of 3D medical images. We use a selector which incorporates the knowledge related to a segmentation model performance measured by the Dice similarity coefficient on a validation dataset. The selector identifies failed validation cases and searches for potentially unsuccessful cases in the unlabeled pool by maximizing a localized image similarity metric. The method is evaluated on two datasets of medical images from multiple sites and modalities: 479 pediatric brain magnetic resonance images for the segmentation of the anterior visual pathway and 131 contrast-enhanced computed tomography scans for liver and tumor segmentation. Our results demonstrate that the proposed AL strategy achieves similar or better segmentation performance than established but computationally more complex uncertainty sampling methods, while showcasing its potential to efficiently select optimal unlabeled data.

Adolescents and young adults (AYAs; ages 15-39 years) are a vulnerable population facing challenges in oncological care, including access to specialized care, transition of care, unique tumor biology, and poor representation in clinical trials. Brain tumors are the second most common tumor type in AYA, with malignant brain tumors being the most common cause of cancer-related death. The 2021 WHO Classification for central nervous system (CNS) Tumors highlights the importance of integrated molecular characterization with histologic diagnosis in several tumors relevant to the AYA population. In this position paper from the Society for Neuro-Oncology (SNO), the diagnosis and management of CNS tumors in AYA is reviewed, focusing on the most common tumor types in this population, namely glioma, medulloblastoma, ependymoma, and CNS germ cell tumor. Current challenges and future directions specific to AYA are also highlighted. Finally, possible solutions to address barriers in the care of AYA patients are discussed, emphasizing the need for multidisciplinary and collaborative approaches that span the pediatric and adult paradigms of care, and incorporating advanced molecular testing, targeted therapy, and AYA-centered care.

Bevacizumab treatment is associated with imaging and hearing responses in progressive vestibular schwannoma (VS) caused by NF2-related schwannomatosis (NF2-SWN). However, its effect on co-existing intracranial non-vestibular schwannomas (NVS) and meningiomas is unclear. We retrospectively analyzed tumor volumes of non-target intracranial NVS and meningiomas in patients with NF2-SWN and progressive VS who were prospectively treated with bevacizumab for two years on the Neurofibromatosis Clinical Trials Consortium (NFCTC) trial NF104 (NCT01767792). Radiographic response (RR) or progression (PD) were defined as ≥ 20