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Adrenocortical cancers in childhood are very rare tumors. They are categorized as functional (hormone-secreting) or silent and as either benign or malignant. They have a bimodal distribution. Although in most adults they are non- functional, in the pediatric age group they may present as hormonal active or as an active tumor presenting with either virilizing forms or Cushing's syndrome or both sometimes. In children, due to the rapid development of symptoms, they come to attention early. However, if not diagnosed and treated early, they can develop into serious medical conditions. We present here a 6-year-old girl complaining of voice changes (deepening), extremely overweight, excessive hair growth over her body, and clitoromegaly for one year. Abdominal ultrasound and computed tomography revealed a well-defined adrenal mass with a slightly heterogeneous appearance and heterogeneous-contrast enhancement containing some necrotic areas. The patient was discharged one week after unilateral right adrenalectomy in good condition, and oral medications were given along with high-dose corticosteroid medications, which were reduced gradually. All the symptoms disappeared 6 months after the operation. Keywords: childhood adrenocortical carcinoma, Cushing's syndrome, virilizing tumors' pediatric cancers

The use of theragnostic radiopharmaceuticals in nuclear medicine has grown rapidly over the years to combine the diagnosis and therapy of tumors. In this review, we performed web-based and desktop literature research to investigate and explain the potential role of theragnostic imaging in pediatric oncology. We focused primarily on patients with aggressive malignancies such as neuroblastoma and brain tumors, to select patients with the highest chance of benefit from personalized therapy. Moreover, the most critical and groundbreaking applications of radioimmunotherapy in children’s oncology were examined in this peculiar context. Preliminary results showed the potential feasibility of theragnostic imaging and radioimmunotherapy in pediatric oncology. They revealed advantages in the management of the disease, thereby allowing an intra-personal approach and adding new weapons to conventional therapies.

Pediatric neurological tumors are a heterogeneous group of cancers, many of which carry a poor prognosis and lack a “standard of care” therapy. While they have similar anatomic locations, pediatric neurological tumors harbor specific molecular signatures that distinguish them from adult brain and other neurological cancers. Recent advances through the application of genetics and imaging tools have reshaped the molecular classification and treatment of pediatric neurological tumors, specifically considering the molecular alterations involved. A multidisciplinary effort is ongoing to develop new therapeutic strategies for these tumors, employing innovative and established approaches. Strikingly, there is increasing evidence that lipid metabolism is altered during the development of these types of tumors. Thus, in addition to targeted therapies focusing on classical oncogenes, new treatments are being developed based on a broad spectrum of strategies, ranging from vaccines to viral vectors, and melitherapy. This work reviews the current therapeutic landscape for pediatric brain tumors, considering new emerging treatments and ongoing clinical trials. In addition, the role of lipid metabolism in these neoplasms and its relevance for the development of novel therapies are discussed.

Purpose Atypical teratoid/rhabdoid tumors (AT/RTs) are malignant central nervous system (CNS) neoplasms of the young. Our study analyzed a large AT/RT cohort from the National Cancer Database (NCDB) to elucidate predictors of short-term mortality and overall survival (OS). Methods Information was collected on patients with histologically confirmed AT/RT using the NCDB (2004–2016). Kaplan–Meier analysis indicated OS. Prognostic factors for 30-day mortality, 90-day mortality, and OS were determined via multivariate Cox proportional hazards (CPH) and logistic regression models. Results Our cohort of 189 patients had a median age of 1 year (IQR [1, 4]) and tumor size of 4.7 ± 2.0 cm at diagnosis. Seventy-two percent were under 3 years old; 55.6% were male and 71.0% were Caucasian. Fifty (27.2%) patients received only surgery (S) (OS = 5.91 months), 51 (27.7%) received surgery and chemotherapy (S + CT) (OS = 11.2 months), and 9 (4.89%) received surgery and radiotherapy (S + RT) (OS = 10.3 months). Forty-five (24.5%) received S + CT + RT combination therapy (OS = 45.4 months), 13 (17.1%) received S + CT + BMT/SCT (bone marrow or stem cell transplant) (OS = 55.5 months), and 16 (8.70%) received S + CT + RT + BMT/SCT (OS = 68.4 months). Bivariate analysis of dichotomized age (HR = 0.550, 95% CI [0.357, 0.847], p  = 0.0067) demonstrated significantly increased patient survival if diagnosed at or above 1 year old. On multivariate analysis, administration of S + CT + RT, S + CT + BMT/SCT, or S + CT + RT + BMT/SCT combination therapy predicted significantly ( p  < 0.05) increased OS compared to surgery alone. Conclusion AT/RTs are CNS tumors where those diagnosed under 1 year old have a significantly worse prognosis. Our study demonstrates that while traditional CT, RT, and BMT/SCT combination regimens prolong life, overall survival in this population is still low.

Purpose of Review Pediatric renal tumors comprise a wide range of conditions, both malignant and benign, that affect children and require a multidisciplinary approach for optimal diagnosis and treatment. This review offers an in-depth analysis of the epidemiology, diagnosis, treatment options, outcomes, and survival of major pediatric renal tumors. Recent Findings Wilms tumor, or nephroblastoma, is the most common form of renal tumor in children, characterized by growth from primitive renal cells. Standard treatment involves a combination of surgery, chemotherapy and, in some cases, radiation therapy, with the aim of removing the tumor, preventing recurrence and maximizing the chances of long-term recovery. Less common pediatric renal tumors, such as renal clear cell sarcoma, renal cell carcinoma, mesoblastic nephroma, and malignant rhabdoid tumor, require similarly careful and individualized management. Therapeutic strategies, which depend on the characteristics of the tumor, the stage of the disease and the individual response to therapy, may include surgery, chemotherapy, radiotherapy and, in some cases, molecular targeted therapies, immunotherapies and genetic and epigenetic therapies. Summary The management of pediatric kidney tumors requires the involvement of a multidisciplinary team of specialists to ensure accurate evaluation, optimal treatments and long-term follow-up. The aim is to maximize the prospects for recovery and improve the quality of life of patients and their families. Advances in innovative, personalized therapies represent an important opportunity to further improve clinical outcomes in these patients.

Analysis of the genomes, exomes and transcriptomes of 1,699 childhood cancers identifies 142 driver genes. Genomic landscape of childhood cancers The genetic alterations that give rise to childhood cancer are less well studied than those that give rise to adult cancers. Two papers in this issue report some of the first pan-cancer analyses of childhood cancers. Stefan Pfister and colleagues studied germline and somatic genomes from 914 young cancer patients, including children, adolescents and young adults. The tumour samples comprised 24 distinct molecular cancer types, including the most frequent and clinically relevant childhood cancers. The team characterized somatic mutation frequencies, genomic alterations, including structural variations and copy-number analysis, and mutational signatures. They found signatures associated with deficiencies of double-stranded break repair across all cancer types. Additionally, 7.6% of patients carried a likely pathogenic germline variant in a candidate cancer predisposition gene. Jinghui Zhang and colleagues analysed the genomes, exomes and transcriptomes of 1,699 paediatric leukaemias and solid tumours. They identified 142 driver genes in paediatric cancers, over half of which were specific to a single histotype. They also characterized copy number alterations and structural variation and identified 11 mutational signatures. Together, these papers provide a comprehensive resource for genomic alterations across common paediatric tumours, and highlight differences compared with the genomic alterations seen in adult cancers. Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been performed for adult 1 , 2 , 3 , 4 but not paediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues 5 . Here we present a pan-cancer study of somatic alterations, including single nucleotide variants, small insertions or deletions, structural variations, copy number alterations, gene fusions and internal tandem duplications in 1,699 paediatric leukaemias and solid tumours across six histotypes, with whole-genome, whole-exome and transcriptome sequencing data processed under a uniform analytical framework. We report 142 driver genes in paediatric cancers, of which only 45% match those found in adult pan-cancer studies; copy number alterations and structural variants constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukaemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for paediatric cancers and emphasize the need for paediatric cancer-specific development of precision therapies.

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and ‘enhancer hijacking’ events that activate PRDM6 . Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma. Genomic analysis of 491 medulloblastoma samples, including methylation profiling of 1,256 cases, effectively assigns candidate drivers to most tumours across all molecular subgroups. Genomic landscapes of medulloblastomas Medulloblastomas are highly malignant brain tumours that develop during childhood. Paul Northcott and colleagues analysed the whole-genome sequences of 491 medulloblastomas in order to characterize the genomic landscape across tumours and identify new drivers and mutational signatures. Their integrative genomic analyses, including methylation profiling of 1,256 medulloblastomas, identifies subgroup-specific driver mutations and suggests additional tumour subtypes. The authors assign driver mutations to a high proportion of the less well characterized Group 3 and Group 4, which together contribute to more than 60% of all medulloblastomas.

Objective Recent therapeutic advances have greatly enhanced the survival rates of patients with neuroblastoma (NB). However, the outcomes of neuroblastoma patients in China, particularly those with high-risk (HR) NB, remain limited. Method We retrospectively analyzed the clinical data and outcomes of NB patients who were treated at a tertiary pediatric cancer facility in China between January 2013 and October 2021. Results A total of 117 NB patients were recruited. Patients with very low-risk (VLR), low-risk (LR), intermediate-risk (IR), and HR-NB patients made up 4%, 27%, 15%, and 54% of total patient population, respectively. Patients diagnosed between 2013 and 2018 were treated according to the protocol of Sun Yat-Sen University Cancer Center and those diagnosed between 2019 and 2021 were treated according to the COG ANBL0531 or ANBL0532 protocol with or without autologous stem cell transplantation (ASCT). The 5-year EFS and OS of all risk groups of patients were 67.29% and 77.90%, respectively. EFS and OS were significantly decreased in patients with higher risk classifications (EFS: VLR/LR vs IR vs HR: 97.22% vs 67.28% vs 51.83%; ***P = .001; OS: VLR/LR vs IR vs HR: 97.06% vs 94.12% vs 64.38%; *P = .046). In HR-NB patients treated according to the COG protocol between 2019 and 2021, the 3-year OS of patients who received tandem ASCT was significantly greater than those who did not receive ASCT (93.33% % vs 47.41%; *P = .046; log-rank test). EFS was not significantly different between patients with and without ASCT (72.16% vs 60.32%). Conclusion Our findings show that patients with lower risk classification have a positive prognosis for survival. The prognosis of patients with HR-NB remains in need of improvement. ASCT may enhance OS in HR-NB patients; however, protocol adjustment may be necessary to increase EFS in these patients.

Introduction Standardisation of imaging acquisition is essential in facilitating multicentre studies related to childhood CNS tumours. It is important to ensure that the imaging protocol can be adopted by centres with varying imaging capabilities without compromising image quality. Materials and method An imaging protocol has been developed by the Brain Tumour Imaging Working Group of the European Society for Paediatric Oncology (SIOPE) based on consensus among its members, which consists of neuroradiologists, imaging scientists and paediatric neuro-oncologists. This protocol has been developed to facilitate SIOPE led studies and regularly reviewed by the imaging working group. Results The protocol consists of essential MRI sequences with imaging parameters for 1.5 and 3 Tesla MRI scanners and a set of optional sequences that can be used in appropriate clinical settings. The protocol also provides guidelines for early post-operative imaging and surveillance imaging. The complementary use of multimodal advanced MRI including diffusion tensor imaging (DTI), MR spectroscopy and perfusion imaging is encouraged, and optional guidance is provided in this publication. Conclusion The SIOPE brain tumour imaging protocol will enable consistent imaging across multiple centres involved in paediatric CNS tumour studies.

Immunotherapy has seen tremendous strides in the last decade, acquiring a prominent position at the forefront of cancer treatment since it has been proven to be efficacious for a wide variety of tumors. Nevertheless, while immunotherapy has changed the paradigm of adult tumor treatment, this progress has not yet been translated to the pediatric solid tumor population. For this reason, alternative curative therapies are urgently needed for the most aggressive pediatric tumors. In recent years, oncolytic virotherapy has consolidated as a feasible strategy for cancer treatment, not only for its tumor-specific effects and safety profile but also for its capacity to trigger an antitumor immune response. This review will summarize the current status of immunovirotherapy to treat cancer, focusing on pediatric solid malignancies. We will revisit previous basic, translational, and clinical research and discuss advances in overcoming the existing barriers and limitations to translate this promising therapeutic as an every-day cancer treatment for the pediatric and young adult populations.