[This corrects the article DOI: 10.3389/fonc.2022.879167.].

The connection and causality between cancer and neurodevelopmental disorders have been puzzling. How can the same cellular pathways, proteins, and mutations lead to pathologies with vastly different clinical presentations? And why do individuals with neurodevelopmental disorders, such as autism and schizophrenia, face higher chances of cancer emerging throughout their lifetime? Our broad review emphasizes the multi-scale aspect of this type of reasoning. As these examples demonstrate, rather than focusing on a specific organ system or disease, we aim at the new understanding that can be gained. Within this framework, our review calls attention to computational strategies which can be powerful in discovering connections, causalities, predicting clinical outcomes, and are vital for drug discovery. Thus, rather than centering on the clinical features, we draw on the rapidly increasing data on the molecular level, including mutations, isoforms, three-dimensional structures, and expression levels of the respective disease-associated genes. Their integrated analysis, together with chromatin states, can delineate how, despite being connected, neurodevelopmental disorders and cancer differ, and how the same mutations can lead to different clinical symptoms. Here, we seek to uncover the emerging connection between cancer, including pediatric tumors, and neurodevelopmental disorders, and the tantalizing questions that this connection raises.

Pediatric low grade brain tumors and neurodevelopmental disorders share proteins, signaling pathways, and networks. They also share germline mutations and an impaired prenatal differentiation origin. They may differ in the timing of the events and proliferation. We suggest that their pivotal distinct, albeit partially overlapping, outcomes relate to the cell states, which depend on their spatial location, and timing of gene expression during brain development. These attributes are crucial as the brain develops sequentially, and single-cell spatial organization influences cell state, thus function. Our underlying premise is that the root cause in neurodevelopmental disorders and pediatric tumors is impaired prenatal differentiation. Data related to pediatric brain tumors, neurodevelopmental disorders, brain cell (sub)types, locations, and timing of expression in the developing brain are scant. However, emerging single cell technologies, including transcriptomic, spatial biology, spatial high-resolution imaging performed over the brain developmental time, could be transformational in deciphering brain pathologies thereby pharmacology.

OBJECTIVE: Peripheral nerve sheath tumors (PNSTs) are rare in pediatric patients, especially in the brachial plexus. Research on PNSTs is lacking. This article presents a retrospective cohort study of pediatric patients diagnosed and treated with PNSTs, specifically brachial plexus tumors.
METHODS: All pediatric patients intervened in a single center between 2007 and 2023 with brachial plexus tumors were systemically analyzed.
RESULTS: Eleven pediatric patients with 14 brachial plexus PNSTs were studied. The gender distribution was 64% female and 36% male, with an average age of 10.7 years. Ninety-one percent had a previous NF-1 diagnosis. Right brachial plexus presented a higher prevalence (64%). Pain, Tinel\'s sign, and stiffness masses were common during diagnosis. Motor deficits were noted in 43% of the patients. Surgery was indicated for symptoms, particularly pain and rapid growth, increasing malignancy risk. Due to suspected malignancy, an en bloc resection with safety margins was performed. Among the patients, 57% received a histopathological diagnosis of MPNST (malignant peripheral nerve sheath tumor). Treatment included radiotherapy and chemotherapy. Clinical follow-up was conducted for all cases, involving clinical and oncological evaluations for all MPNSTs.
CONCLUSIONS: This article present a series of pediatric brachial plexus tumors, especially in NF-1, and emphasizes the importance of thorough evaluation for this group. Swift diagnosis is crucial in pediatrics, enabling successful surgery for small lesions with limited neurological symptoms, improving long-term outcomes. Prompt referral to specialized services is urged for suspected masses, irrespective of neurological symptoms. Benign tumor postsurgical progression shows better outcomes than MPNSTs, with complete resection as the primary goal. Needle-guided biopsy is not recommended.

Myoepithelial tumors of the soft tissue and bone occurring in patients 21 years of age and younger are rare, and their clinicopathologic features remain incompletely understood. We studied a well-characterized series of 40 such tumors. Cases were retrieved from our archives for the period 2009-2022 and re-reviewed. Available immunohistochemical and molecular genetic data was collected. Clinical information including available follow-up was obtained. The tumors occurred in 18 males and 22 females, ranging from 3 months to 21 years of age (median 11.5 years), and involved a wide variety of soft tissue (n = 36) and bone (n = 4) locations. Histologically benign myoepithelial tumors tended to occur in adolescents (median age 14.5 years; range 5-21 years), whereas myoepithelial carcinomas occurred in younger patients (median age 8.5 years; range 3 months-20 years). Microscopically, the tumors showed a complex admixture of epithelioid, plasmacytoid and spindled cells in a variably hyalinized, myxoid, chondroid or chondromyxoid background. Small subsets of histologically malignant tumors had rhabdoid or \"round cell\" features. Immunohistochemistry showed 35/40 (88%) cases to be positive with at least one keratin antibody. The 5 keratin-negative tumors were uniformly positive for S100 protein and/or SOX10 and expressed EMA (4 cases) and/or p63 (3 cases). EMA, SMA and GFAP were positive in 21/25 (84%), 13/21 (62%), and 8/21 (38%) tumors, respectively. SMARCB1 and SMARCA4 expression was retained in 29/31 (94%) and 22/22 (100%) of cases, respectively. FISH for EWSR1 gene rearrangement was positive in 6/18 (33%) tested cases. Two EWSR1-negative tumors were also FUS-negative. NGS identified EWSR1::POU5F1, FUS::KLF17, and BRD4::CITED1 gene fusions in 3 tested cases. Clinical follow-up (22 patients; median 23 months; range 1-119 months) showed 3 patients with local recurrences and 5 with distant metastases (lymph nodes, lung, and brain). Three patients died of disease, 3 were alive with recurrent or unresectable disease, and 16 were disease-free. Adverse clinical outcomes were seen only in patients with malignant tumors. We conclude that myoepithelial neoplasms of soft tissue and bone are over-repesented in patients ≤21 years of age, more often histologically malignant, and potentially lethal. Histologic evaluation appears to reliably predict the behavior of these rare tumors.

The promising results seen in the treatment of refractory hematologic malignancies with tisagenlecleucel (Kymriah), the pioneering Chimeric Antigen Receptor (CAR) T-cell immunotherapy, has stimulated a fast growth in research and clinical testing of novel CAR-T constructs, targets, and various generations of CAR T-cells. Pharmacists may receive inquiries about active clinical trials or may be contributing to the care of patients participating in these studies. This briefing discusses the on-going clinical trials that explore novel CAR T-cell immunotherapies in pediatric refractory malignancies of hematologic and solid organ origins. It can be valuable in assisting practitioners in navigating the rapidly evolving field of CAR T-cell immunotherapies.

BACKGROUND: Pineal region tumors have historically been challenging to treat. Advances in surgical techniques have led to significant changes in care and outcomes for these patients, and this is well demonstrated by our single institution\'s experience over a 17-year-period in which the evolution of diagnosis, treatment, and outcomes of pineal tumors in pediatric patients will be outlined.
METHODS: We retrospectively collected data on all pediatric patients with pineal region lesions treated with surgery at Children\'s National Hospital (CNH) from 2005 to 2021. Variables analyzed included presenting symptoms, presence of hydrocephalus, diagnostic and surgical approach, pathology, and adverse events, among others. IRB approval was obtained (IRB: STUDY00000009), and consent was waived due to minimal risk to patients included.
RESULTS: A total of 43 pediatric patients with pineal region tumors were treated during a 17-year period. Most tumors in our series were germinomas (n = 13, 29.5%) followed by pineoblastomas (n = 10, 22.7%). Twenty seven of the 43 patients (62.8%) in our series received a biopsy to establish diagnosis, and 44.4% went on to have surgery for resection. The most common open approach was posterior interhemispheric (PIH, transcallosal) - used for 59.3% of the patients. Gross total resection was achieved in 50%; recurrence occurred in 20.9% and mortality in 11% over a median follow-up of 47 months. Endoscopic third ventriculostomy (ETV) was employed to treat hydrocephalus in 26 of the 38 patients (68.4%) and was significantly more likely to be performed from 2011 to 2021. Most (73%) of the patients who received an ETV also underwent a concurrent endoscopic biopsy. No difference was found in recurrence rate or mortality in patients who underwent resection compared to those who did not, but complications were more frequent with resection. There was disagreement between frozen and final pathology in 18.4% of biopsies.
CONCLUSIONS: This series describes the evolution of surgical approaches and outcomes over a 17-year-period at a single institution. Complication rates were higher with open resection, reinforcing the safety of pursuing endoscopic biopsy as an initial approach. The most significant changes occurred in the preferential use of ETVs over ventriculoperitoneal shunts. Though there has been a significant evolution in our understanding of and treatment for these tumors, in our series, the outcomes for these patients have not significantly changed over that time.

OBJECTIVE: As survival rates in childhood cancer progress significantly, health outcomes in adulthood are pivotal to quality of life (QoL). Female patients undergoing chemotherapy and radiation for childhood cancer may experience adverse effects such as gonadotoxicity-related ovarian insufficiency. Ovarian tissue cryopreservation (OTC) is well studied in adults, but has only recently started to be explored in an effort to preserve fertility in young patients with childhood cancer. This systematic review aims to critically highlight contemporary outcomes of cryopreservation in female pediatric cancer patients.
METHODS: A systematic search was conducted in PubMed, Embase, and Web of Science databases to identify English-language full text articles and abstracts published between 2004 and 2022 describing cryopreservation among female children (0-21 years old) with cancer. Abstracts and full-text articles were screened for inclusion. Subsequently, data from eligible studies was extracted and analyzed. Descriptive statistics were utilized to estimate overall outcomes of cryopreservation.
RESULTS: Of 104 abstracts and 34 full-text articles, 12 studies were included. Data was collected from 7 world countries and involved some 612 pediatric and adolescent patients with malignant disease. Most common cancers included hematological malignant disease (81%), CNS nervous system malignant tumors (56%), and sarcomas (39%). Of the 6 studies with full reporting, OTC was undertaken in 501 patients, and 5.9% (30/501) of these patients underwent ovarian tissue transplantation (OTT). After OTT, 27 patients desired pregnancy and 33% (9/27) became pregnant. Six of these 9 patients (67%) had live births.
CONCLUSIONS: Preliminary analysis showed that OTC has been successfully performed but not yet studied thoroughly in pediatric cancer patients in a longitudinal manner. This study has further shown that cryopreservation outcomes are mainly reported among adult patients living in high income countries, demonstrating a crucial need for long-term outcome studies focused on pediatric and prepuberal OTC, subsequent OTT, and potential pregnancy. This work is considered critical to aid standardize recommendations of fertility preservation in childhood cancer patients and to better inform the efficacy of these procedures to benefit patients in world nations of all fiscal income levels.
METHODS: Level III.

OBJECTIVE: Robot-assisted biopsies have gained popularity in the last years. Most robotic procedures are performed with a floor-based robotic arm. Recently, Medtronic Stealth Autoguide, a miniaturized robotic arm that work together with an optical neuronavigation system, was launched. Its application in pediatric cases is relatively unexplored. In this study, we retrospectively report our experience using the Stealth Autoguide, for frameless stereotactic biopsies in pediatric patients.
METHODS: Pediatric patients who underwent stereotactic biopsy using the Stealth Autoguide cranial robotic platform from July 2020 to May 2023 were included in this study. Clinical, neuroradiological, surgical, and histological data were collected and analyzed.
RESULTS: Nineteen patients underwent 20 procedures (mean age was 9-year-old, range 1-17). In four patients, biopsy was part of a more complex surgical procedure (laser interstitial thermal therapy - LITT). The most common indication was diffuse intrinsic brain stem tumor, followed by diffuse supratentorial tumor. Nine procedures were performed in prone position, eight in supine position, and three in lateral position. Facial surface registration was adopted in six procedures, skull-fixed fiducials in 14. The biopsy diagnostic tissue acquisition rate was 100% in the patients who underwent only biopsy, while in the biopsy/LITT group, one case was not diagnostic. No patients developed clinically relevant postoperative complications.
CONCLUSIONS: The Stealth Autoguide system has proven to be safe, diagnostic, and highly accurate in performing stereotactic biopsies for both supratentorial and infratentorial lesions in the pediatric population.

The family of the neurotrophic tyrosine kinase receptor (NTRK) gene encodes for members of the tropomyosin receptor kinase (TRK) family. Rearrangements involving NTRK1/2/3 are rare oncogenic factors reported with variable frequencies in an extensive range of cancers in pediatrics and adult populations, although they are more common in the former than in the latter. The alterations in these genes are causative of the constitutive activation of TRKs that drive carcinogenesis. In 2017, first-generation TRK inhibitor (TRKi) larotrectinib was granted accelerated approval from the FDA, having demonstrated histologic-agnostic activity against NTRKs fusions tumors. Since this new era has begun, resistance to first-generation TRKi has been described and has opened the development of second-generation molecules, such as selitrectinib and repotrectinib. In this review, we provide a brief overview of the studies on NTRK alterations found in pediatric central nervous system tumors and first and second-generation TRKi useful in clinical practice.