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Central nervous system (CNS) tumours in neonates are relatively rare and present differently when compared with those occurring later in childhood in terms of aetiology, clinical features, location, histology and prognosis. The clinical presentation is extremely variable. Even if the most frequent clinical sign is a macrocephaly, there are many other non-specific symptoms associated. The prognosis is usually poor with overall survival of less than 30%. Surgery continues to be the primary treatment for neonatal CNS tumours, aiming for a gross total resection, directly correlated with prognosis and the overall outcome. The chemotherapy is the only adjuvant therapy whereas the radiotherapy is avoided under three years of age because of the severe sequelae. Hence the importance of molecular characterization of these neoplasms in order to improve the accuracy of the diagnosis and identify new therapeutic targets. The aim of this review is to describe the main characteristics of these tumours and the recent advances in their treatment in order to recognize these pathologies in the prenatal period and create a multidisciplinary team providing the best possible treatment while minimising the risk of long-term complications. Neonatologists play a key role in the early detection, diagnostic evaluation, management and supportive care of these neonates. Conclusion: The aim of this review is to describe the main characteristics of these tumours and the recent advances in their treatment in order to ensure the essential knowledge that will help the neonatologist identify them and create a multidisciplinary team providing the best possible treatment while minimising the risk of long-term complications. What is Known: • Neonatal CNS tumours are relatively rare and their early identification is important to identify the best diagnostic-therapeutic management. • Surgery is the main treatment of neonatal CNS tumours. The extent of surgical resection directly correlates with prognosis and outcome. What is New: • Predisposing conditions such as Cancer Predisposition Syndromes must be considered. • Targeted drugs and other therapeutic strategies can be identified through molecular characterization [ABSTRACT FROM AUTHOR]

Background: Germ cell tumors (GCT) account for a minority of central nervous system (CNS) malignancies, highly prevalent in adolescents and young adults. Despite their aggressive biological behavior, prognosis is excellent in most cases with risk stratified treatment, consisting in a combination of chemotherapy and radiotherapy. Whole ventricular irradiation (WVI) and craniospinal irradiation, the treatment of choice for localized and metastatic disease, pose significant risk of collateral effects, therefore proton beam radiation (PBT) has been recently proposed for its steep dose fallout. Materials and methods: We report our experience in a consecutive series of 17 patients treated for CNS GCT at our Institution from 2015 to 2021. Results: Most frequent lesion location were sellar/suprasellar (35%) and bifocal germinoma (35%), followed by pineal (18%) and thalamic (12%). Two patients (12%), had evidence of disseminated disease at the time of diagnosis. At the latest follow-up all but one patient showed complete response to treatment. The only relapse was successfully rescued by additional chemotherapy and PBT. PBT was well tolerated in all cases. No visual, neurological or endocrinological worsening was documented during and after treatment. Neuropsychological evaluation demonstrated preservation of cognitive performance after PBT treatment. Conclusions: Our data, albeit preliminary, strongly support the favourable therapeutic profile of PBT for the treatment of CNS germ cell tumors. [ABSTRACT FROM AUTHOR]

Background: This systematic review has been conducted with the aim of characterizing cognitive deficits and analyzing their frequency in survivors of paediatric Central Nervous System tumours. Materials and methods: All literature published up to January 2023 was retrieved searching the databases "PubMed", "Cochrane", "APA PsycInfo" and "CINAHL". The following set of pre-defined inclusion criteria were then individually applied to the selected articles in their full-text version: i) Retrospective/prospective longitudinal observational studies including only patients diagnosed with primary cerebral tumours at = 21 years (range 0-21); ii) Studies including patients evaluated for neuro-cognitive and neuro-psychological deficits from their diagnosis and/or from anti-tumoral therapies; iii) Studies reporting standardized tests evaluating patients' neuro-cognitive and neuro-psychological performances; iv) Patients with followups = 2 years from the end of their anti-tumoral therapies; v) Studies reporting frequencies of cognitive deficits. Results: 39 studies were included in the analysis. Of these, 35 assessed intellectual functioning, 30 examined memory domains, 24 assessed executive functions, 22 assessed attention, 16 examined visuo-spatial skills, and 15 explored language. A total of 34 studies assessed more than one cognitive function, only 5 studies limited their analysis on a single cognitive domain. Attention impairments were the most recurrent in this population, with a mean frequency of 52.3% after a median period post-treatment of 11.5 years. The other cognitive functions investigated in the studies showed a similar frequency of impairments, with executive functions, language, visuospatial skills and memory deficits occurring in about 40% of survivors after a similar post-treatment period. Longitudinal studies included in the systematic review showed a frequent decline over time of intellectual functioning. Conclusions: Survivors of paediatric Central Nervous System tumours experience cognitive sequelae characterized by significant impairments in the attention domain (52.3%), but also in the other cognitive functions. Future studies in this research field need to implement more cognitive interventions and effective, but less neurotoxic, tumour therapies to preserve or improve neurocognitive functioning and quality of life of this population. [ABSTRACT FROM AUTHOR]

Although there are several immunotherapy approaches for the treatment of Central Nervous System (CNS) tumors under evaluation, currently none of these approaches have received approval from the regulatory agencies. CNS tumors, especially glioblastomas, are tumors characterized by highly immunosuppressive tumor microenvironment, limiting the possibility of effectively eliciting an immune response. Moreover, the peculiar anatomic location of these tumors poses relevant challenges in terms of safety, since uncontrolled hyper inflammation could lead to cerebral edema and cranial hypertension. The most promising strategies of immunotherapy in neuro-oncology consist of the use of autologous T cells redirected against tumor cells through chimeric antigen receptor (CAR) constructs or genetically modified T-cell receptors. Trials based on native or genetically engineered oncolytic viruses and on vaccination with tumor-associated antigen peptides are also under evaluation. Despite some sporadic complete remissions achieved in clinical trials, the outcome of patients with CNS tumors treated with different immunotherapeutic approaches remains poor. Based on the lessons learned from these unsatisfactory experiences, novel immune-therapy approaches aimed at overcoming the profound immunosuppressive microenvironment of these diseases are bringing new hope to reach the cure for CNS tumors. [ABSTRACT FROM AUTHOR]

Summary: Relapses involving the central nervous system (CNS) are rare in children and adolescents with ALK+ anaplastic large cell lymphoma (ALCL) treated with regimens including CNS prophylaxis. Early identification of patients at high‐risk for CNS relapse would enable stratification and better adaptation of initial treatment especially in the light of the upcoming targeted therapies with limited CNS penetration. We analyzed clinical and histological data of all ALK+ALCL patients with CNS relapse registered in ALCL99‐database with the aim to describe risk factors and outcome. Characteristics of patients with no relapse, relapse without CNS involvement and CNS relapse were compared. At a median follow‐up of 8 years (0.05–18 years), a CNS involvement was reported at first or subsequent relapse in 26/618 patients. Median interval between initial diagnosis and first CNS relapse was 8 months (IQR 5.55–10.61/range 1.31–130.69). The 5‐year cumulative risk of CNS relapse was 4% (95% CI 2.9–5.5). Bone marrow involvement, peripheral blasts and CNS involvement at diagnosis were more frequent in patients with CNS relapse than in patients with no relapse or with relapse with no CNS involvement. The treatment of CNS relapse was heterogeneous. The median survival after CNS relapse was 23.7 months. Eleven patients were alive at last follow‐up. Three‐year overall survival after CNS relapse was 48.70% (95% CI 30.52–67.23). [ABSTRACT FROM AUTHOR]

Rhabdoid tumors are rare aggressive malignancies in infants and young children with a poor prognosis. The most common anatomic localizations are the central nervous system, the kidneys, and other soft tissues. Rhabdoid tumors share germline and somatic mutations in SMARCB1 or, more rarely, SMARCA4 , members of the SWI/SNF chromatin-remodeling complex. Rhabdoid tumor predisposition syndrome (RTPS) is a condition characterized by a high risk of developing rhabdoid tumors, among other features. RTPS1 is characterized by pathogenic variants in the SMARCB1 gene, while RTPS2 has variants in SMARCA4. Interestingly, germline variants of SMARCB1 and SMARCA4 have been identified also in patients with Coffin-Siris syndrome. Children with RTPS typically present with tumors before 1 year of age and in a high percentage of cases develop synchronous or multifocal tumors with aggressive clinical features. The diagnosis of RTPS should be considered in patients with rhabdoid tumors, especially if they have multiple primary tumors and/or in individuals with a family history. Because germline mutations result in an increased risk of carriers developing rhabdoid tumors, genetic counseling, and surveillance for all family members with this condition is recommended. [ABSTRACT FROM AUTHOR]

The determination of Human Chorionic Gonadotropin (hCG) and Alpha Fetoprotein (AFP) levels on serum and amniotic fluid plays a fundamental role in the diagnosis and follow-up of specific physiological or pathological conditions (e.g., pregnancy, threat of abortion or germ cell tumors). Recently, the quantification of hCG and AFP in other biological fluids has gained great attention to support the diagnosis, prognosis and follow-up of neoplastic diseases deriving from trophoblastic cells, such as germinomas. Most of the commercial kits for hCG and AFP assays are developed to be used on biological fluids such as serum/plasma and/or urine by manufacturing companies. The aim of this work was to evaluate the suitability of the analytical method certified for the use on serum, and/or amniotic fluid for the quantification of hCG and AFP in cerebrospinal fluid, carrying out an internal validation protocol. The data reported here show that the automated immunochemical method is fit for quantification of hCG and AFP in cerebrospinal fluid (CSF), allowing selective and specific diagnosis of secreting germ cell tumors. This is confirmed by the positive correlation between elevated levels of hCG or AFP and the diagnosis of brain tumors. [ABSTRACT FROM AUTHOR]

Brain tumors are the most common solid neoplasms of childhood. They are frequently reported in children with Neurofibromatosis type 1 (NF1). The most frequent central nervous system malignancies described in NF1 are optic pathway gliomas and brainstem gliomas. Medulloblastoma (MB) in NF1 patients is extremely rare, and to our knowledge, only 10 cases without molecular characterization are described in the literature to date. We report the case of a 14-year-old girl with NF1 that came to our attention for an incidental finding of a lesion arising from cerebellar vermis. The mass was completely resected, revealing a localized classic medulloblastoma (MB), subgroup 4. She was treated as a standard-risk MB with a dose-adapted personalized protocol. The treatment proved to be effective, with minor toxicity. Brain and spine MRI one year after diagnosis confirmed the complete remission of the disease. To our knowledge, this is the only case of MB reported in a patient with NF1 with molecular characterization by the methylation profile. The association between NF1 and MB, although uncommon, may not be an accidental occurrence. [ABSTRACT FROM AUTHOR]