Pediatric brain tumors are the leading cause of childhood cancer-related death. Immunotherapy is a powerful new approach for treating some refractory cancers; applying this 'fourth pillar' of cancer treatment to pediatric brain tumors is an exciting but challenging prospect. This review offers new perspectives on moving towards successful immunotherapy for pediatric brain tumors, focusing on pediatric high-grade glioma (HGG), a subgroup with universally poor outcomes. We cover chimeric antigen receptor T cell (CAR-T) therapy, vaccine therapy, and checkpoint inhibition in this context, and focus on the need for intimately understanding the growing brain and its immune system. We highlight the challenges associated with the application of immunotherapy in pediatric neuro-oncology, as well as the tissue-specific challenges to be overcome, to achieve improved outcomes. Immunotherapy: A New Approach for Pediatric Brain Tumors Recent advances in cancer immunotherapy have improved outcomes for several human cancers, and in some cases have produced dramatic responses in patients refractory to all other conventional modes of treatment [1-3]. Although the concept of strengthening, redirecting, or generating an immune response against malignancy is by no means new, cancer immunotherapy has only recently received worldwide attention. Immunotherapy has demonstrated remarkable success in improving overall survival in Phase II-III trials in tumor subtypes such as melanoma and leukemia [1,4]. This novel approach has been a welcome addition to the oncologist's conventional armamentarium of surgery, chemotherapy, and radiation, especially in the relapsed and/or refractory disease setting. This rapid advancement in the immuno-oncology field occurs in a timely manner for childhood brain tumors, which urgently require a new approach. Tumors of the central nervous system (CNS) are the most common solid tumor of childhood, and represent the leading cause of childhood cancer-related death [5]. Although survival rates for childhood cancers overall have markedly improved over recent decades, outcomes in pediatric CNS tumors have lagged behind the dramatic gains achieved in hematological cancers. The overall survival rate in childhood acute lymphoblastic leukemia now exceeds 90% at 5 years [6]. In stark contrast, children with pediatric high-grade glioma (HGG; see Glossary), including diffuse midline glioma (DMG), and glioblastoma multiforme (GBM), have a dismal 5 year overall survival of b20% [6]. This occurs despite recent increased knowledge of the genomics of pediatric HGG and how this diverges markedly from adult brain tumors [7], and multiple trials of differing combinations of radiation, chemotherapeutic agents, and novel adjuvants. Furthermore, given that current conventional treatments involve irradiation of the brain, the few survivors of pediatric brain tumors are often left with devastating morbidities, including endocrine disease, psychiatric, cognitive and developmental disorders, and neurological disease, as well as a high i...

Background: Invasive fungal infections (IFI) are an important complication of acute lymphoblastic leukaemia (ALL) treatment. Our study describes the prevalence and outcomes of IFI in children with ALL. Methods: IFI episodes in children with primary or relapsed ALL, identified for The Epidemiology and Risk Factors for Invasive Fungal Infections in Immunocompromised Children study, were analysed. IFI were classified according to European Organization for Research and Treatment of Abbreviations: ALL, acute lymphoblastic leukaemia; CCG, Children'

Abtract Background This study describes imaging features of diffuse intrinsic pontine glioma (DIPG) and correlates with overall survival (OS) and histone mutation status in the International DIPG Registry (IDIPGR). Methods Four hundred cases submitted to the IDIPGR with a local diagnosis of DIPG and baseline MRI were evaluated by consensus review of 2 neuroradiologists; 43 cases were excluded (inadequate imaging or alternative diagnoses). Agreement between reviewers, association with histone status, and univariable and multivariable analyses relative to OS were assessed. Results On univariable analysis imaging features significantly associated with worse OS included: extrapontine extension, larger size, enhancement, necrosis, diffusion restriction, and distant disease. On central review, 9.5% of patients were considered not to have DIPG. There was moderate mean agreement of MRI features between reviewers. On multivariable analysis, chemotherapy, age, and distant disease were predictors of OS. There was no difference in OS between wild-type and H3 mutated cases. The only imaging feature associated with histone status was the presence of ill-defined signal infiltrating pontine fibers. Conclusions Baseline imaging features are assessed in the IDIPGR. There was a 9.5% discordance in DIPG diagnosis between local and central review, demonstrating need for central imaging confirmation for prospective trials. Although several imaging features were significantly associated with OS (univariable), only age and distant disease were significant on multivariable analyses. There was limited association of imaging features with histone mutation status, although numbers are small and evaluation exploratory.