Pseudoprogression in Pediatric Spinal Pilocytic Astrocytoma and Myxopapillary Ependymoma after Proton Therapy: A Case Series.

Background: Little is known about pseudoprogression after proton therapy (PT) for pediatric spinal tumors. Clinical consequences are significant if it is not appropriately identified. We report the incidence of pseudoprogression in pediatric spinal pilocytic astrocytoma (sPA) and myxopapillary ependymoma (MPE) after PT at our institution.

Pediatric Central Nervous System Cancers, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology.

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.

Phase I Study of Vorinostat and Temsirolimus in Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma.

Background: Diffuse intrinsic pontine glioma (DIPG) carries a poor prognosis with a median survival of less than 12 months. Key molecular features include histone H3 mutation (K27M) and AKT pathway dysregulation. There is currently no curative treatment.

Phase 2 trial of veliparib, local irradiation, and temozolomide in patients with newly diagnosed high-grade glioma: a Children's Oncology Group study.

Background: The outcome for pediatric patients with high-grade glioma (HGG) remains poor. Veliparib, a potent oral poly(adenosine diphosphate-ribose) polymerase (PARP) 1/2 inhibitor, enhances the activity of radiotherapy and DNA-damaging chemotherapy.

Methods: We conducted a single-arm, non-randomized phase 2 clinical trial to determine whether treatment with veliparib and radiotherapy, followed by veliparib and temozolomide, improves progression-free survival in pediatric patients with newly diagnosed HGG without H3 K27M or BRAF mutations, compared to patient-level data from historical cohorts with closely matching clinical and molecular features.

Marrow-ablative consolidation chemotherapy and molecular targeted therapy delivered in a risk-adapted manner for newly diagnosed children with choroid plexus carcinoma: .

Choroid plexus carcinomas (CPC) are early childhood cancers characterized by loss of function and poor survival. We are analyzing data on status, survival, and second cancers from the largest cohort of CPC receiving chemotherapy followed by consolidation with marrow-ablative chemotherapy (HDCx). Additionally, we discuss the rationale for targeted therapies for CPC patients.

Safety and pharmacokinetics of ONC201 (dordaviprone) administered two consecutive days per week in pediatric patients with H3 K27M-mutant glioma.

Background: This study evaluated the safety and pharmacokinetics (PK) of oral ONC201 administered twice-weekly on consecutive days (D1D2) in pediatric patients with newly diagnosed DIPG and/or recurrent/refractory H3 K27M glioma.

Methods: This phase 1 dose-escalation and expansion study included pediatric patients with H3 K27M-mutant glioma and/or DIPG following ≥1 line of therapy (NCT03416530). ONC201 was administered D1D2 at 3 dose levels (DLs; -1, 1, and 2).

Retrospective Analysis of Imaging Characteristics of Tectal Gliomas.

Background And Purpose: Tectal gliomas (TGs) are rare tumors that involve critical locations in the brainstem, including the superior and inferior colliculi and the Sylvian aqueduct. The rarity of these tumors and the lack of large clinical studies have hindered adequate understanding of this disease. We sought to determine the association between imaging characteristics of TG and progression-free survival (PFS).

Phase I dose escalation and expansion trial of single agent ONC201 in pediatric diffuse midline gliomas following radiotherapy.

Background: ONC201, a dopamine receptor D2 (DRD2) antagonist and caseinolytic protease P (ClpP) agonist, has induced durable tumor regressions in adults with recurrent H3 K27M-mutant glioma. We report results from the first phase I pediatric clinical trial of ONC201.

Methods: This open-label, multi-center clinical trial (NCT03416530) of ONC201 for pediatric H3 K27M-mutant diffuse midline glioma (DMG) or diffuse intrinsic pontine glioma (DIPG) employed a dose-escalation and dose-expansion design.

Contrast Enhancement Patterns in Pediatric Glioblastomas.

Background And Purpose: Brain tumors are the most common cause of cancer-related deaths among the pediatric population. Among these, pediatric glioblastomas (GBMs) comprise 2.9% of all central nervous system tumors and have a poor prognosis.

Sleep Disturbance and Its Association With Sluggish Cognitive Tempo and Attention in Pediatric Brain Tumor Survivors.

Background: Pediatric brain tumor (PBT) survivors are at risk for developing sleep disturbances. While in other pediatric populations sleep disturbance has been associated with worse cognitive functioning, it is unclear to what extent this relationship generalizes to PBT survivors. The aim of the current study was to assess the relationship between sleep disturbance and aspects of cognition, including sluggish cognitive tempo (SCT) as well as attention and working memory.

Quantifying the risk and dosimetric variables of symptomatic brainstem injury after proton beam radiation in pediatric brain tumors.

Background: Brainstem toxicity after radiation therapy (RT) is a devastating complication and a particular concern with proton radiation (PBT). We investigated the incidence and clinical correlates of brainstem injury in pediatric brain tumors treated with PBT.

Methods: All patients <21 years with brain tumors treated with PBT at our institution from 2007-2019, with a brainstem Dmean >30 Gy and/or Dmax >50.

Reevaluating surgery and re-irradiation for locally recurrent pediatric ependymoma-a multi-institutional study.

Background: The goal of this study was to evaluate extent of surgical resection, and timing and volume of re-irradiation, on survival for children with locally recurrent ependymoma.

Methods: Children with locally recurrent ependymoma treated with a second course of fractionated radiotherapy (RT2) from 6 North American cancer centers were reviewed. The index time was from the start of RT2 unless otherwise stated.

Prognostic Value of Cell-Surface Vimentin-Positive CTCs in Pediatric Sarcomas.

Background: Despite advances in care, the 5 year overall survival for patients with relapsed and or metastatic sarcoma remains as low as < 35%. Currently, there are no biomarkers available to assess disease status in patients with sarcomas and as such, disease surveillance remains reliant on serial imaging which increases the risk of secondary malignancies and heightens patient anxiety.

Methods: Here, for the first time reported in the literature, we have enumerated the cell surface vimentin (CSV+) CTCs in the blood of 92 sarcoma pediatric and adolescent and young adult (AYA) patients as a possible marker of disease.

Case series of diffuse extraneural metastasis in H3F3A mutant high-grade gliomas: Clinical, molecular phenotype and literature review.

H3K27M and H3.3G34R/V mutations have been identified in pediatric high-grade gliomas (pHGG), though extraneural metastases are rarely reported and poorly characterized. Three pHGG patients from two institutions were identified with extraneural metastasis, harboring histone mutations.

Observed-to-expected incidence ratios of second malignant neoplasms after radiation therapy for medulloblastoma: A Surveillance, Epidemiology, and End Results analysis.

Background: The authors analyzed the incidence and types of second malignant neoplasms (SMNs) in patients treated for medulloblastoma.

Methods: The authors compared the incidence of SMNs after radiotherapy (RT) for medulloblastoma in patients treated in 1973-2014 with the incidence in the general population with the multiple primary-standardized incidence ratio function of Surveillance, Epidemiology, and End Results 9. Observed-to-expected incidence (O/E) ratios and 95% confidence intervals (CIs) were reported for the entire cohort and by disease site according to age at diagnosis, treatment era, and receipt of chemotherapy.

Case Discussion and Literature Review: Cancer Immunotherapy, Severe Immune-Related Adverse Events, Multi-Inflammatory Syndrome, and Severe Acute Respiratory Syndrome Coronavirus 2.

Pediatric, adolescent and young adult (AYA) patients receiving novel cancer immunotherapies may develop associated toxicities with overlapping signs and symptoms that are not always easily distinguished from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/clinical sequelae. We describe 2 diagnostically challenging cases of SARS-CoV-2 and Multi-Inflammatory Syndrome-Adult (MIS-A), in patients with a history of acute lymphoblastic leukemia following cellular therapy administration and review evolving characterization of both the natural course of SARS-CoV-2 infection and toxicities experienced in younger cancer immunotherapy patients. Vigilant monitoring for unique presentations and epidemiologic surveillance to promptly detect changes in incidence of either condition may be warranted.