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Despite advances in treatment options, the clinical outcomes of pediatric patients with advanced solid tumors have hardly improved in decades, and alternative treatment options are urgently needed. Innovative therapies, such as chimeric antigen receptor (CAR) T cells and oncolytic viruses (OVs), are currently being evaluated in both adults and children with refractory solid tumors. Because pediatric solid tumors are remarkably diverse and biologically different from their adult counterparts, more research is required to develop effective treatment regimens for these patients. Here, we first summarize recent efforts and advances in treatments for pediatric solid tumors. Next, we briefly introduce the principles for CAR T cell therapy and oncolytic virotherapy and clinical trials thereof in pediatric patients. Finally, we discuss the basis for the potential benefits of combining the two approaches in pediatric patients with advanced solid tumors.

BackgroundPediatric 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.Materials and MethodsEighty-three PBT survivors 6–18 years of age who were at least 3 months post-treatment were included in the present cross-sectional study. Level of sleep disturbance was measured as a composite score reflecting various sleep problems as rated by caregivers. Cognitive measures included caregiver-ratings of sluggish cognitive tempo and attention problems, as well as performance-based cognitive measures assessing attention and executive functioning. Hierarchical regression analysis was used to assess associations between sleep and cognition.ResultsOf all caregivers, 32.5% reported one or more sleep disturbances as “very/often true” and over 68% of caregivers rated at least one sleep-related item as “somewhat true.” Of all cognitive variables, scores were most frequently impaired for SCT (30%). A higher level of sleep disturbance was associated with worse SCT and parent-rated attention problems. Associations between sleep and performance-based cognitive measures assessing attention and working memory were not statistically significant.ConclusionFindings of the current study highlight the importance of further investigation into the relationship between sleep and cognition in PBT survivors, which may assist efforts to maximize cognitive outcome and health-related quality of life in PBT survivors. The current study additionally suggests further investigation of SCT in this population is warranted, as it may be more sensitive to detecting possible associations with sleep disturbance relative to discrete measures that assess cognitive performance under ideal circumstances.

BackgroundDespite 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.MethodsHere, 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.ResultsWe constructed a ROC with an AUC of 0.831 resulting in a sensitivity of 85.3% and a specificity of 75%. Additionally, patients who were deemed to be CSV+ CTC positive were found to have a worse overall survival compared to those who were CSV+ CTC negative. We additionally found the use of available molecular testing increased the accuracy of our diagnostic and prognostic tests.ConclusionsOur findings indicate that CSV+ CTCs have prognostic value and can possibly serve as a measure of disease burden.

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.

Pediatric high-grade glioma (pHGG) and brainstem gliomas are some of the most challenging cancers to treat in children, with no effective therapies and 5-year survival at ~2% for diffuse intrinsic pontine glioma (DIPG) patients. The standard of care for pHGG as a whole remains surgery and radiation combined with chemotherapy, while radiation alone is standard treatment for DIPG. Unfortunately, these therapies lack specificity for malignant glioma cells and have few to no reliable biomarkers of efficacy. Recent discoveries have revealed that epigenetic disruption by highly conserved mutations in DNA-packaging histone proteins in pHGG, especially DIPG, contribute to the aggressive nature of these cancers. In this review we pose unanswered questions and address unexplored mechanisms in pre-clinical models and clinical trial data from pHGG patients. Particular focus will be paid towards therapeutics targeting chromatin modifiers and other epigenetic vulnerabilities that can be exploited for pHGG therapy. Further delineation of rational therapeutic combinations has strong potential to drive development of safe and efficacious treatments for pHGG patients.