Surveillance magnetic resonance imaging (MRI) is routinely used to detect recurrence in pediatric central nervous system (CNS) tumors. The frequency of neuroimaging surveillance varies without a standardized approach. A single-institutional retrospective cohort study evaluated the frequency of recurrences. This study included 476 patients with the majority diagnosed with low-grade glioma (LGG) (n=138, 29%), high-grade glioma (HGG) (n=77, 16%), ependymoma (n=70, 15%), or medulloblastoma (n=61, 13%). LGG, HGG, and ependymoma patients more commonly had multiply recurrent disease (P=0.08), with ependymoma patients demonstrating ≥2 relapses in 47% of cases. Recurrent disease was identified by imaging more often than clinical symptoms (65% vs. 32%; P=10 years from initial diagnosis. With a higher tendency toward detection of tumor recurrence/progression on MRI surveillance in comparison to clinical progression, surveillance imaging is necessary in routine follow up of pediatric CNS tumor survivors. With some relapses >10 years from initial diagnosis, imaging beyond this time point may be useful in particular tumor types. While the study is limited in outcome analysis, earlier detection of recurrence would lead to earlier initiation of treatment and implementation of salvage treatment regimens which can impact survival and quality of life.

Utilizing a Scoping Review strategy in the domain of immune biology to identify immune therapeutic targets, knowledge gaps for implementing immune therapeutic strategies for pediatric brain tumors was assessed. The analysis demonstrated limited efforts to date to characterize and understand the immunological aspects of tumor biology with an over-reliance on observations from the adult glioma population. Foundational knowledge regarding the frequency and ubiquity of immune therapeutic targets is an area of unmet need along with the development of immune-competent pediatric tumor models to test therapeutics and especially combinatorial treatment. Opportunities arise in the evolution of pediatric tumor classification from histological to molecular with targeted immune therapeutics.

Therapy‐related myeloid neoplasms (t‐MN) are a distinct subgroup of myeloid malignancies with a poor prognosis that include cases of therapy‐related myelodysplastic syndrome (t‐MDS), therapy‐related myeloproliferative neoplasms (t‐MPN) and therapy‐related acute myeloid leukemia (t‐AML). Here, we report a series of patients with clinical features consistent with juvenile myelomonocytic leukemia (JMML), an overlap syndrome of MDS and myeloproliferative neoplasms that developed after treatment for another malignancy.

Background: Children and adolescents with cancer may experience multiple disease- and treatment-related symptoms that negatively affect health-related quality of life. Routine symptom surveillance thus constitutes an important component of supportive care in pediatric oncology. The Symptom Monitoring and Systematic Assessment and Reporting System in Young Survivors (SyMon-SAYS) system will administer, score, interpret, and display the results of symptom assessments captured weekly using patient-reported outcomes presented via the electronic health record (EHR) portal between clinic visits in oncology ambulatory settings, when patients are likely to be more symptomatic. This study is testing a digital system for routine symptom surveillance that includes EHR-based reports to clinicians and alerts for severe symptoms. Objective: In this randomized trial, we are examining the effects of the SyMon-SAYS system on perceived barriers to symptom management, self-efficacy, and symptom severity. Better self-management and timely clinical intervention to address symptoms promote adherence to treatment plans, strengthen child and parent self-efficacy, improve interactions between children, parents, and their clinical providers, and optimize clinical outcomes. Methods: The SyMon-SAYS system is integrated into the EHR to streamline the presentation of symptom scores and delivery of alerts for severe symptoms to clinicians using EHR (Epic) messaging functionalities. Children (aged 8 to 17 years) complete the weekly symptom assessment and review the symptom report by logging into the patient portal (Epic MyChart). This single-institution waitlist randomized controlled trial is recruiting 200 children (aged 8-17 years) with cancer and their parents, guardians, or caregivers. Participating dyads are randomly assigned to receive the intervention over 16 weeks (Group A: 16-week SyMon-SAYS intervention; Group B: 8-week usual care and then an 8-week SyMon-SAYS intervention). Analyses will (1) evaluate the efficacy of SyMon-SAYS at week 8 and the maintenance of those effects at week 16; (2) evaluate factors associated with those efficacy outcomes, including contextual factors, adherence to the SyMon-SAYS intervention, demographic characteristics, and clinical factors; and (3) evaluate predictors of adherence to the SyMon-SAYS intervention and preference of SyMon-SAYS versus usual care. Results: Data collection is currently in progress. We hypothesize that at 8 weeks, those receiving the SyMon-SAYS intervention will report decreased parent-perceived barriers to managing their children’s symptoms, increased parent and child self-efficacy, decreased child symptom burden, and ultimately better child health-related quality of life, compared to waitlist controls. Feasibility, acceptability, and engagement from the perspectives of the children with cancer, their parents, and their clinicians will be examined using mixed methods. Conclusions: We anticipate that this system will facilitate prompt identification of problematic symptoms. Additionally, we hypothesize that with the availability of graphical symptom reports over time, and timely provider responses, children or parents will become better informed and take an active role in managing their symptoms, which will further improve clinical outcomes. Trial Registration: ClinicalTrials.gov NCT04789720; https://clinicaltrials.gov/study/NCT04789720 International Registered Report Identifier (IRRID): DERR1-10.2196/50993

Purpose: The PBTC-051 study is the first pediatric evaluation of a CD40 agonist and assessed the safety, pharmacokinetics, and preliminary efficacy of sotigalimab in children and young adults with recurrent or progressive malignant central nervous system (CNS) tumors (stratum 1) and post-radiation pre-progression diffuse intrinsic pontine glioma (DIPG) (stratum 2). Patients and methods: This prospective phase 1 study conducted by the Pediatric Brain Tumor Consortium evaluated sotigalimab using a 3+3 design for dose escalation. Immune pharmacodynamics were assessed with RNA transcript analysis, T cell receptor sequencing, and cytokine profiling. Results: 31 eligible patients were enrolled (stratum 1: 20, stratum 2: 11). The stratum 1 recommended phase 2 dose was 0.6 mg/kg every 3 weeks; the stratum 2 maximum tolerated dose was 0.3 mg/kg every 3 weeks. Five patients had dose-limiting toxicities. No patients had an objective response. For stratum 1, 6-month and 12-month progression-free survivals (PFS) were 13.3% (standard error [SE], 8.1%) and 6.7% (SE, 6.2%), respectively; for stratum 2, 6-month PFS and overall survival were 31.2% (SE, 14.8%) and 44.4% (SE, 16.6%), respectively. At all dose levels, the maximum serum concentration was reached at the end of infusion; no drug accumulation was detected. More than 40% of patients developed anti-drug antibodies. Signaling pathways associated with activated antigen presenting cells and T cells were enriched in patients with higher PFS, while increased loss of heterozygosity was noted in patients with lower PFS. Conclusions: Sotigalimab was well-tolerated in pediatric patients with recurrent or progressive CNS tumors and post-radiation pre-progression DIPG.