Abstract Background Pediatric low-grade gliomas (LGGs) often harbor alterations in the MAP kinase pathway. Targeted therapy, including MEK inhibitors, have been increasingly used for patients with incompletely resected and relapsed LGGs. Nevertheless, patients still need several lines of therapy for refractory and progressive tumors. Preclinical studies have suggested combination MEK and mTOR pathway inhibition may be synergistic, however, adult clinical trials have raised concerns over the associated toxicity. Case presentation Patient 1 was a 24-year-old male with suprasellar KIAA1549-BRAF fused pilocytic astrocytoma previously treated with single agent carboplatin, trametinib, a failed re-trial of trametinib, and substantial progression through tovorafenib. After further progression, he started trametinib (0.025 mg/kg/day) and everolimus (2 mg/m2/day). Within 10 months, the tumor has remained stable by RAPNO LGG criteria but showed substantial reduction in extensive surrounding T2/FLAIR signal. Dose reductions were necessary due to symptomatic peripheral edema and mucositis. Patient 2 was a 7-year-old girl with an NF-1 associated optic pathway glioma (with FGFR1 mutation) who has been on therapy since age 1. Interventions included vinblastine, carboplatin/vincristine, MEK inhibitor, mTOR inhibitor, retrial of MEK inhibitor, Avastin, and clinical trial with poly-ICLC. She started trametinib (0.025 mg/kg/day) and everolimus 2 mg/m2/day 5 days on, 2 off). Over 13 months, she had stable disease (minimally decreased in size). Fifty percent dose reduction of trametinib was required due to surgical site wound infection. Conclusion Combination therapy with trametinib and everolimus has stabilized two refractory LGGs who were previously treated with MEKi therapy and failed to respond to retreatment. Treatment has been well tolerated after initial dose reductions.

BackgroundDrugs that target the mitogen-activated protein kinase pathway have caused frequent and significant skin toxicity, which has led to increased burden on both patients and their caregivers. Routine skin care products for daily use have been shown to improve skin toxicity. If a patient is provided with basic skin care products for daily use this could facilitate skin management while on these medications.MethodParticipants 0-21 years old who were treated with any medication targeting the mitogen-activated protein kinase (MAPK) pathway were eligible for this prospective, single-site study. Each participant received a complimentary skin care kit consisting of skin, hair, and oral care items. The utilization of these skin care kits was evaluated and participant satisfaction with the items was measured. Secondarily, the participants' quality of life (QOL) was assessed and the participants' adherence to their MAPK inhibitor was evaluated.ResultsSeventeen participants (10 male, 7 female) with a median age of 10.5 years were enrolled. Forty-seven percent of participants rated their satisfaction with the kit as excellent, and no patient rated it as poor. Seventy-seven percent of participants rated the kit helpful, and the majority (76.5%) thought the kits should be distributed before the initiation of therapy. QOL changes were not statistically significant.ConclusionsParticipants on MAPK inhibitors who received skin care kits were satisfied with the kits' ability to help with their skin side effects. Given the high satisfaction and acceptability, future studies should evaluate the effect of these kits on QOL with adequate power to detect improvements.

Abstract Background Adolescents and young adults (AYAs), ages 15–39, with central nervous system (CNS) tumors often fall between pediatric and adult oncology systems, leading to fragmented care and missed opportunities for clinical trial participation. These gaps contribute to disparities in treatment access and long-term outcomes. Methods A centralized, nursing-led AYA Neuro-Oncology Clinical Trial Referral Program was implemented at our institution for adolescent and young adult patients aged 18–39 years. Nurses served as primary coordinators, participating in multidisciplinary tumor boards and adult oncology clinical trial meetings to prospectively identify eligible patients. A designated Research Nurse functioned as the AYA Clinical Trial Coordinator, providing centralized communication, systematic eligibility screening, coordination with disease-specific research teams, and timely feedback to referring providers. Results Following implementation, pediatric neuro-oncology consultations for AYA patients increased by 142%, from 7 patients over 2020–2024 to 17 patients in 2025 alone. Clinical trial enrollment increased fivefold, with 5 AYA patients enrolling in 2025 compared to only one patient in the prior five-year period. Conclusion Implementation of a nurse-supported AYA Neuro-Oncology referral and clinical trial coordination model led to substantial improvements in patient identification, interdisciplinary communication, and trial enrollment. These findings support the development of a dedicated AYA Neuro-Oncology program, with nursing leadership playing a critical role in ensuring continuity of care and equitable access to clinical trials across the care continuum. Broader dissemination of this model may help standardize care transitions and expand trial access for AYA patients across diverse practice settings.

Abstract Introduction Glucose utilization by tumors has been studied as a potential target to exploit in treating malignancies. FDG-PET has demonstrated that FDG uptake in brain tumors positively correlates with brain tumor grade and poorer prognosis and is also used as modality for staging in solid tumors due to increased glycolytic index of the tumors. Sodium glucose cotransporter 2 inhibitors (SGLT2i), such as dapagliflozin, lower serum glucose by inhibiting reabsorption in the renal tubules.Additionally, tumors also express functional SGLT2 on their cell surface, indicating that SGLT2i may have direct glycolytic inhibitory effects on brain and solid tumors. Methods Patients with relapsed/refractory brain or solid tumors with no curative options were enrolled to a 12-week trial of dapagliflozin in addition to cytotoxic chemotherapy including BCNU (100 mg/m2 every 6 weeks) for brain tumor patients and topotecan (0.75 mg/m2) with cyclophosphamide (250 mg/m2) on days 1-5 of 21 day cycles for solid tumor patients. Patients aged 6-12 years received a fixed dapagliflozin dose of 5 mg daily, while patients aged 11-21 years began at 5 mg and escalated to 10 mg after two weeks if well tolerated. Imaging was performed every 6 weeks. Results To date, we have enrolled four patients aged 7-17 years (two anaplastic ependymomas, one high grade glioma, one Ewing sarcoma). Two patients had stable disease (ependymoma and Ewing sarcoma) and two had progressive disease. There were no Grade 3 or 4 toxicities related to dapagliflozin. One patient had Grade 1 ketoacidosis in the setting of poor caloric intake. Of note, one patient with anaplastic ependymoma continued dapagliflozin and BCNU for 1 year with continued stable disease. Conclusions Adding SGLT2i with dapagliflozin to cytotoxic chemotherapy for relapsed/refractory brain and solid tumors has thus far been well tolerated and two patients demonstrated stable disease. Enrollment in this study is ongoing.

BACKGROUND:Group 4 medulloblastoma (MB) is rare in young children. Data on craniospinal irradiation (CSI)-sparing approaches are limited. METHODS:This multicenter study reported outcomes for patients younger than 7 years old with Group 4 MB treated with high-dose chemotherapy (HDC) without adjuvant CSI. RESULTS:Thirty-eight patients were included (26 M/12 F). Median age at diagnosis was 46.4 months (25.9-78), with 24% ≤36 months. Twenty-four patients (63.2%) had localized disease. Fourteen (36.8%) presented with metastatic disease, and 26 (68.4%) underwent gross total resection (GTR). The most used HDC regimens were carboplatin/thiotepa (76.3%) and carboplatin/thiotepa/etoposide (21.1%). Twenty (52.6%) relapses occurred at a median 21.9 months (5-99.8) from diagnosis. Patients with upfront GTR and/or who received three cycles of HDC had better PFS (p = 0.02 and p = 0.002, respectively). Local relapse accounted for 45%. Eighteen patients received salvage therapy with curative intent, all with radiotherapy (16 = CSI, 2 = focal). The CSI dose ranged from 18 to 36 Gy, and 43.7% received ≤23.4 Gy. Patients who underwent salvage surgery and/or chemotherapy were more likely to receive CSI ≤23.4 Gy (p = 0.008 and p = 0.03). The 5-year post-relapse survival and overall survival (OS) were, respectively, 60.3% (95% confidence interval [CI]: 26.9-82) and 72.7% (95% CI: 51.9-85.7). The 5-year CSI-free OS was 69.7% (95% CI: 39.1-87.1). CONCLUSION:High dose chemotherapy for Group 4 MB was associated with a relapse rate of 52.6%, which favorably compares to data reported with conventional chemotherapy. Salvage radiotherapy retrieved more than two-thirds of the patients. Half of the survivors never received radiotherapy. Such an approach may represent an alternative to upfront CSI for young children with Group 4 MB.

Abstract Background Weight loss is one of the most common and challenging complications typically encountered during and after therapy for patients diagnosed with medulloblastoma. Nevertheless, its incidence and management strategies have been rarely reported. Methods A single institution retrospective analysis was conducted to characterize changes in weight and body mass index (BMI) before, during and after therapy in pediatric patients diagnosed with medulloblastoma. Secondary objectives included exploring the efficacy of weight management interventions and associated complications. Results A total of 35 patients were included. Age at diagnosis ranged from 4-20 years. Sixty percent received treatment per ACNS0331 and 40% per ACNS0332. All patients treated per ACNS0332 and 90.5% treated as per ACNS0331 experienced weight loss during therapy. At the end of treatment , only 57.1% of those treated per ACNS0331 and 42.9% of those treated per ACNS0332 had returned to their baseline weight. Most BMIs were categorized as underweight at baseline, throughout therapy, and until 1-year post-therapy. Within 5 years post completion of therapy, 56.5% of the patients had a healthy BMI. While 6–10-years after therapy 54.5% of patients were categorized as overweight or obese. A variety of weight management therapies were trialed. Megestrol outperformed all other interventions, followed by enteral feeding. Of those who received megestrol, 50% developed adrenal insufficiency while on megestrol and the remainder after discontinuing megestrol. Conclusion BMI and weight changes, whether gain or loss, should be carefully assessed and addressed before therapy begins and monitored across the lifespan to support the best possible outcomes for a healthy weight and lifestyle. Although megestrol was effective for weight gain, it should be used with caution in this population given the high incidence of adrenal insufficiency.

Abstract Background Group 4 medulloblastoma (MB) are rare in young children and their outcome when treated with radiation avoidance strategies is unknown. Method This retrospective international cohort included children with molecularly characterized group 4 treated with high-dose chemotherapy(HDC) and CSI sparing approach. Results The cohort includes 38 patients (26M/12F) diagnosed at a median age of 46.4 months (25.9-78). Twenty-four (63.2%) were M0 and 26(68.4%) underwent initial gross total resection. The most common consolidation used was three cycles of HDC (carboplatin, thiotepa) in 76.3% or one cycle of HDC (carboplatin, etoposide, thiotepa) in 21.1%. Twenty patients (52.6%) relapsed at a median time of 24.9 months from diagnosis, providing a 5 years PFS of 40.9%(±9.2%). Patients who underwent 3 cycles of HDC, who received carboplatin and thiotepa or who achieved complete response at treatment completion had a better PFS. High-dose methotrexate during induction and metastatic status did not impact PFS. Relapse was local in 45%. Eighteen patients underwent radiation-based salvage therapy (2 focal, 16 CSI) in intent to cure. The median dose of CSI was 36 Gy (18-36). However, 7(43.7%) patients received CSI dose< 24 Gy. The 5 years post-relapse survival was 60.3% (±14.8%). At median follow-up of 39.9 months from diagnosis, 29 (76.3%) patients were alive, seven died of disease and two of toxicity, leading to 5 years OS of 72.7% (±8.6%). Using the SIOP-Boston scale, grades 2, 3 and 4 ototoxicity were reported in 18.7%, 31.2% and 25%. Mean FSIQ for patients without relapse or evaluated prior relapse was 86.5 (range 69-97; N = 6) and 2 had age appropriate cognitive and intellectual skills. Conclusions HDC and CSI sparing approaches led to a high rate of relapse (52.6%). However, 72.2% patients were salvaged with radiation-based therapy given at a median time of 2 years after initial diagnosis.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Central Nervous System Cancers provide multidisciplinary diagnostic workup, staging, and treatment recommendations for diffuse high-grade gliomas and medulloblastomas in children and adolescents. This article summarizes the studies and panel discussion that serve as the rationale for comprehensive care recommendations included in the NCCN Guidelines for Pediatric Central Nervous System Cancers.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Central Nervous System Cancers provide multidisciplinary diagnostic workup, staging, and treatment recommendations for diffuse high-grade gliomas and medulloblastomas in children and adolescents. This article summarizes the studies and panel discussion that serve as the rationale for comprehensive care recommendations included in the NCCN Guidelines for Pediatric Central Nervous System Cancers.

Background:Central nervous system tumors are the leading cause of cancer-related mortality in children, with significant disparities in diagnostic and treatment capabilities between low- and middle-income countries and high-income countries. This study outlines the establishment of an international neuro-oncology tumor board to address these gaps. Methods:The tumor board was initiated in January 2021 through a partnership between Washington University in St. Louis, USA, and nine institutions, ultimately expanding to 39 institutions across 25 countries. Monthly virtual meetings facilitated multidisciplinary case reviews offering diagnostic and management recommendations. A retrospective analysis of 29 sessions over three years was conducted, and a cross-sectional web-based survey among participants assessed their experiences and satisfaction. Results:From January 2021 to December 2023, 101 cases were reviewed. The most diagnoses were low-grade gliomas (23.4%) and neurofibromatosis type 1 and 2 (32.7%). Newly diagnosed cases comprised 51%, while 40% involved recurrent or progressive disease, and 9% were inquiries during ongoing therapy. Recommendations predominantly addressed therapeutic strategies (60.7%). Advanced diagnostics, such as methylation profiling, refined diagnoses in several cases. The survey, with a 35% response rate, showed high satisfaction, with 91% finding the meetings educational. Barriers included time constraints (71%) and conflicting commitments (27%). Conclusion:This initiative, to our knowledge, represents the largest international pediatric neuro-oncology tumor board. Multidisciplinary discussions improved diagnostic precision, informed therapeutic decision-making and facilitated educational exchange. Participants reported positive impacts on professional development and alignment with institutional needs. Despite challenges, this study highlights telemedicine's potential to bridge resource disparities and improve the outcomes globally.

Abstract BACKGROUND Supratentorial neuroepithelial tumor with PLAGL1 fusion has emerged as a novel subgroup within pediatric brain tumors. Despite its recent identification, critical aspects such as optimal clinical characteristics and management strategies remain elusive. This case report aims to contribute essential insights to the growing body of literature surrounding this enigmatic tumor entity, providing a detailed exploration of its clinical presentation and histopathological features. METHODS A retrospective chart review was conducted, and relevant data were analyzed. RESULTS An 11-year-old female presented with a two-week history of headaches, vomiting, lethargy, and decreased oral intake. Neuroimaging revealed a left frontal lesion with conspicuous mass effect and midline shift, prompting urgent craniotomy due to sudden onset altered mental status. Histopathological analysis revealed a hypercellular glial neoplasm characterized by perivascular pseudorosettes, scattered microcalcifications, microcysts, and areas of necrosis. Immunohistochemical staining revealed GFAP positivity in a substantial subset of tumor cells, rare dot-like positivity for EMA, and diffuse membranous and focal dot-like positivity for D240. Olig2 was mostly negative, indicating the absence of Oligodendrocyte lineage differentiation. The tumor exhibited an elevated Ki-67 proliferation index (approximately 20-30%). Fluorescence in situ hybridization (FISH) studies were negative for RELA, YAP1, and C19MC rearrangements. Targeted next-generation sequencing unveiled an EWSR1-PLAG1 fusion and methylation profiling classified the tumor as “Neuroepithelial tumors, PLAG1-fused” with high confidence. Given the morphological resemblance to anaplastic ependymoma, the therapeutic recommendation included focal irradiation (54 Gy) with proton therapy. The patient, now 12 months post-therapy, is showing favorable clinical outcomes. CONCLUSION This case report underscores the clinical and histopathological intricacies of supratentorial neuroepithelial tumors with PLAGL1 fusion. The identification of EWSR1-PLAG1 fusion and associated molecular alterations informs diagnostic considerations and treatment strategies for this novel entity, emphasizing the importance of continued research to enhance our understanding of its clinical behavior and optimal management approaches.

PURPOSE Histone 3 (H3) K27M–mutant diffuse midline glioma (DMG) has a dismal prognosis with no established effective therapy beyond radiation. This integrated analysis evaluated single-agent ONC201 (dordaviprone), a first-in-class imipridone, in recurrent H3 K27M–mutant DMG. METHODS Fifty patients (pediatric, n = 4; adult, n = 46) with recurrent H3 K27M–mutant DMG who received oral ONC201 monotherapy in four clinical trials or one expanded access protocol were included. Eligible patients had measurable disease by Response Assessment in Neuro-Oncology (RANO) high-grade glioma (HGG) criteria and performance score (PS) ≥60 and were ≥90 days from radiation; pontine and spinal tumors were ineligible. The primary end point was overall response rate (ORR) by RANO-HGG criteria. Secondary end points included duration of response (DOR), time to response (TTR), corticosteroid response, PS response, and ORR by RANO low-grade glioma (LGG) criteria. Radiographic end points were assessed by dual-reader, blinded independent central review. RESULTS The ORR (RANO-HGG) was 20.0% (95% CI, 10.0 to 33.7). The median TTR was 8.3 months (range, 1.9-15.9); the median DOR was 11.2 months (95% CI, 3.8 to not reached). The ORR by combined RANO-HGG/LGG criteria was 30.0% (95% CI, 17.9 to 44.6). A ≥50% corticosteroid dose reduction occurred in 7 of 15 evaluable patients (46.7% [95% CI, 21.3 to 73.4]); PS improvement occurred in 6 of 34 evaluable patients (20.6% [95% CI, 8.7 to 37.9]). Grade 3 treatment-related treatment-emergent adverse events (TR-TEAEs) occurred in 20.0% of patients; the most common was fatigue (n = 5; 10%); no grade 4 TR-TEAEs, deaths, or discontinuations occurred. CONCLUSION ONC201 monotherapy was well tolerated and exhibited durable and clinically meaningful efficacy in recurrent H3 K27M–mutant DMG.

Mitogen-activated protein kinase (MAPK) pathway inhibitors are incorporated into the treatment regimens for several pediatric cancers. However, they commonly trigger dermatologic side effects, which can be challenging to manage and may have a significant impact on the quality of life. We previously performed a prospective study looking at the satisfaction and utilization of skincare kits and patient education regarding basic skincare practices. Based on these data, we developed revised skincare product kits and treatment plans that can be individualized for patients who are at risk of developing dermatologic side effects from targeted therapies. Based on our prior study, 77% of patients thought the skincare kits and instructions were helpful. Seventy-seven percent of patients also recommended that they be distributed at the initiation of therapy. Through this study, we discovered that the patient reported medical history questions were inconsistent when compared with medical chart reviews. The most common discrepancies included information regarding patient’s diagnosis, prescribed medications, skin-related problems, and past medical history. From this data, we have developed a new skincare product kit and patient skincare plans which we distribute to every patient prior to starting their targeted therapy. The skincare kits consist of a cleanser, emollient, oral care products, sunscreen, pyrithione zinc containing shampoo, and facial moisturizers for adolescent patients. Our patient skincare plans consist of patient-specific information including diagnosis, medications, and their targeted agent. The plan provides details on how and when to use each product, application time, and order in which to apply products and topical medications. Our project has highlighted the importance of patient education regarding dermatologic side effects in those starting targeted therapies. We have successfully implemented this by providing our patients with both skincare products and patient-specific care plans.

Abstract BACKGROUND WNT and group 4 medulloblastoma (MB) are rare in young children and their outcome when treated with radiation avoidance infant strategies is unknown. METHOD This retrospective international cohort included children less than 7 years of age, with molecularly characterized group 4 or WNT MB, treated with high-dose chemotherapy(HDC) and CSI sparing approach. RESULTS The current cohort includes 29 patients (19M/10F). For the 26 patients with group 4 MB (median age at diagnosis 45.9 months), 16 (61.5%) were M0 and 17 (65.3%) underwent initial gross total resection (GTR). The most common consolidation regimen used was three cycles of high dose carboplatin and thiotepa (65.5%) or a single cycle of high dose of carboplatin, etoposide and thiotepa (31%).Two received adjuvant focal radiotherapy. Sixteen patients (61.5%) relapsed at a median time of 21.4 months from diagnosis (median age of 5.2 years). Relapse was local for 50% of the patients. One patient underwent palliative management and 15 received radiation-based salvage therapy (2 focal, 13 CSI+/- boost).The median dose of CSI was 36Gy (18-36). Five of the 15 died of disease. Overall, at a median follow-up of 37.9 months from diagnosis, 17/26 (65.3%) patients were alive, six had died of disease and two of toxicity. All 3 WNT patients (median age at diagnosis 57.8 months) underwent GTR and two were M0. Two received sequential high dose carboplatin and thiotepa. One patient with initial partial response, progressed 2 months after treatment completion and received salvaged CSI (18Gy). All of them were alive at a median follow up of 88 months from diagnosis. CONCLUSIONS HDC and CSI sparing approaches led to a high rate of relapse for young patient with group 4 (61.5%). However, 2/3 were salvaged with radiation-based therapy given at a median age 5.2 yrs. Additional WNT patients are needed to better describe their management.