New CNS tumor classification: The importance in pediatric neurosurgical practice.

Background: The management of the central nervous system (CNS) tumors in the pediatric population is crucial in neurosurgical practice. The World Health Organization (WHO) has evolved its classification of CNS tumors from the 19th century to the 5th edition, published in 2021, incorporating molecular advancements. This transition from morphology to molecular characterization is ongoing. Methods: This manuscript analyzes the modifications introduced in the 5th edition of WHO's CNS tumor classification, particularly focusing on pediatric tumor families. The paper integrates clinical, morphological, and molecular information, aiming to guide pediatric neurosurgeons in their daily practice and interdisciplinary discussions. Results: The 5th edition of the WHO classification introduces a hybrid taxonomy that incorporates both molecular and histological components. The terminology shifts from "entity" to "type" and "subtype," aiming to standardize terminology. Tumor grading experiences changes, integrating molecular biomarkers for prognosis. The concept of integrated layered diagnosis is emphasized, where molecular and histological information is combined systematically. Conclusion: The 5th edition of the WHO CNS classification signifies a paradigm shift toward molecular characterization. The incorporation of molecular advances, the layered diagnostic approach, and the inclusion of clinical, morphological, and molecular information aim to provide comprehensive insights into pediatric CNS tumors. This classification offers valuable guidance for pediatric neurosurgeons, aiding in precise diagnosis and treatment planning for these complex neoplasms.

Sexual health in adult survivors of childhood cancer: A Project REACH study.

BACKGROUND: Sexual dysfunction is a significant complication of treatment for many adult-onset cancers. However, comparatively less is known about sexual dysfunction in adult childhood cancer survivors (CCSs). Research has been limited by the exclusion of specific cancers (e.g., central nervous system [CNS] tumors) and the lack of validated measures, which makes it difficult to understand the nature and prevalence of sexual dysfunction in CCSs. METHODS: A total of 249 adult CCSs (aged 18-65 years) enrolled in Project REACH, a prospective cohort study, and completed measures of physical and mental health, including sexual dysfunction. Participants scoring ≤19 on the Female Sexual Function Index 6 or ≤21 on the International Index of Erectile Function 5 were classified as experiencing sexual dysfunction. Analyses examined the relationships between sexual dysfunction and demographic, disease, treatment, and health variables. RESULTS: A total of 78 participants (32%) experienced clinically significant sexual dysfunction. In univariate analysis, sexual dysfunction was significantly associated with CNS tumor diagnosis (odds ratio [OR], 2.56) and surgery (OR, 1.96) as well as with health variables such as fatigue (OR, 3.00), poor sleep (OR, 2.84), pain (OR, 2.04), depression (OR, 2.64), poor physical health (OR, 2.45), and poor mental health (OR, 2.21). Adjusted analyses found that CNS tumor diagnosis (p = .001) and health variables (p = .025) contribute significantly to sexual dysfunction in CCSs. CONCLUSIONS: Approximately one third of adult CCSs report clinically significant sexual dysfunction, which underscores a significant screening and treatment need. However, because available measures were developed for survivors of adult cancers, research to create a sexual health measure specifically for adult CCSs is necessary to better identify the sexual health concerns of this vulnerable population.

Incidence of Pediatric Cancers in French Guiana: How Does It Compare to Global Estimates?

French Guiana is a French territory in South America. The exposome of persons living there is quite different from that in mainland France and the ethnic make-up of the population is also quite different. Poverty is also widespread with difficulties in accessing care magnified by the low medical-professional density. In this singular context, we aimed to measure the incidence of pediatric cancers and to compare it with other continents. We used French Guiana's certified cancer registry to study this between 2003 and 2017. Incidences were standardized using the world population with three strata: 0-4 years, 5-9 years, and 10-14 years. There were 164 solid tumors or hematologic malignancies diagnosed in children under the age of 15 (92 in boys and 72 in girls). Over the study period, the standardized incidence rate was 14.1 per 100,000 among children aged under 15 years. There was no significant trend during the study period. The three most common causes of cancer were leukemias-mostly lymphoblastic-CNS tumors, and sarcoma. The standardized incidence of pediatric cancers in French Guiana was similar to those in Western Europe and North America. As others have discovered, we found that males tended to be more likely to develop cancer, notably leukemia, CNS tumors, sarcoma, and retinoblastoma. As elsewhere, the predominant cancer types changed with age. Our initial assumption was that given the singular context of French Guiana, there may have been differences in pediatric cancer incidences. Here we showed that overall, contrary to our assumption and to trends in tropical countries, the incidence of pediatric cancers was in a range between Western Europe and North America with some apparent but non-significant differences in the main types of cancers observed in global statistics. Quality cancer registry data in this tropical region confirm the suspicion that lower incidences in tropical low- and middle-income countries are likely to result from incomplete diagnosis and data collection.

Factors Influencing Mortality in Children with Central Nervous System Tumors: A Cohort Study on Clinical Characteristics and Genetic Markers.

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098-5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74-35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87-16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915-16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83-15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747-11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831-22.02, p = 0.004, HR = 9.571, 95% CI 2.856-32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669-16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411-13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST.

Clinical roles of EGFR amplification in diffuse gliomas: a real-world study using the 2021 WHO classification of CNS tumors.

Background: The 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates EGFR amplification (Amp) as one of diagnostic markers for glioblastoma (GBM). Purpose: This study aimed to describe the frequency, clinical value and molecular correlation of EGFR Amp in diffuse gliomas based on the latest classification. Methods: We reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of EGFR Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of EGFR Amp in different glioma subtypes. Results: 163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. EGFR Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM. Conclusion: Our study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.

Spinal Cord Medulloepithelioma in a Cat.

A 13-month-old, neutered, male, domestic shorthair cat was referred with a history of progressive paraparesis, proprioceptive ataxia, and lumbar spinal pain. Neurological examination revealed non-ambulatory paraparesis consistent with L4-S1 myelopathy. Magnetic resonance of the thoracolumbar spinal cord identified a dorsal intradural extramedullary space-occupying lesion extending from L5 to L6. It was homogeneously hyperintense in T2-weighted imaging and isointense in T1-weighted imaging and exhibited marked and homogeneous contrast enhancement in the T1-weighted post-contrast imaging. The removed tissue was composed of neoplastic cells arranged as pseudostratified or multilayered trabecular and tubular structures, supported by internal and external limiting PAS-positive membranes. The neoplastic cells were immunoreactive for vimentin and NSE and negative for GFAP, Olig2, synaptophysin, PCK, S-100, NeuN, and nestin. The Ki-67 nuclear labeling index was up to 90%. The tumor was consistent with the diagnosis of medulloepithelioma, which is most frequently reported as an intraocular tumor. The morphological and immunohistochemical features of the tumor showed remarkable concordance with most human medulloepitheliomas. This is the first spinal cord medullopethelioma report in a cat, with the clinical, neuroradiological, histological, and immunohistochemical findings being described.

Cerebrospinal Fluid Liquid Biopsies in the Evaluation of Adult Gliomas.

PURPOSE OF REVIEW: This review aims to discuss recent research regarding the biomolecules explored in liquid biopsies and their potential clinical uses for adult-type diffuse gliomas. RECENT FINDINGS: Evaluation of tumor biomolecules via cerebrospinal fluid (CSF) is an emerging technology in neuro-oncology. Studies to date have already identified various circulating tumor DNA, extracellular vesicle, micro-messenger RNA and protein biomarkers of interest. These biomarkers show potential to assist in multiple avenues of central nervous system (CNS) tumor evaluation, including tumor differentiation and diagnosis, treatment selection, response assessment, detection of tumor progression, and prognosis. In addition, CSF liquid biopsies have the potential to better characterize tumor heterogeneity compared to conventional tissue collection and CNS imaging. Current imaging modalities are not sufficient to establish a definitive glioma diagnosis and repeated tissue sampling via conventional biopsy is risky, therefore, there is a great need to improve non-invasive and minimally invasive sampling methods. CSF liquid biopsies represent a promising, minimally invasive adjunct to current approaches which can provide diagnostic and prognostic information as well as aid in response assessment.

Correlation of progesterone receptors and P63 to the histological grade of meningiomas: Review and significance in an African population.

Objectives: Meningiomas, a common neoplasm of the central nervous system, is a widely studied meningeal tumor. According to the World Health Organization (WHO) 2021 classification of meningiomas, there are 15 subtypes that have been grouped into grades 1, 2, and 3. The WHO grade 1 meningiomas are generally grouped as benign while the WHO grades 2 and 3 tumors are grouped as malignant. Progesterone receptors and P63 are common immunohistochemical markers that have proven useful in the diagnosis, grading, and prognostication of many neoplasms such as breast carcinoma, prostate carcinoma, and gastrointestinal tumors in histopathology practice. The application of these immunohistochemical markers to the grading of meningiomas has been reported and their usefulness documented in reports from Africa, Europe, North America, South America, and Asia. This study, therefore, seeks to determine if these findings are applicable to the meningiomas seen in an African population. Materials and Methods: A 10-year review of results and histologically diagnosed cases of meningiomas received in the Department of Morbid Anatomy, University of Nigeria, Enugu. Immunostaining for progesterone receptors (PgRs) and P63 were done and results compared with histologic grades. Results: The three WHO grades of meningioma were assessed in this study. M: F ratio was 1:1.4 and peak age was 41-50 years age range (SD ± 16.54). The majority of the cases were WHO grade 1 (86.1%) while the WHO grades 2 and 3 tumors were 8% and 5.9%, respectively. The fibrous variant was the most common subtype (27.1%). There was no correlation between progesterone receptor and P63 immunopositivity to the WHO grades of meningioma (P = 0.112 and P = 0.138, respectively). Conclusion: Our study showed that progesterone receptors and P63 immunopositivity did not correlate with the WHO grades of meningiomas. This may be due to the predominant variant of meningioma seen in this study. These findings indicate that PgR antagonist may not be an effective alternative for treatment in patients with inoperable meningiomas. Furthermore, P63 immunopositivity may not be a sufficient grading tool for managing meningiomas in our population.

Registration, incidence patterns, and survival trends of central nervous system tumors among children in Germany 1980-2019: An analysis of 40 years based on data from the German Childhood Cancer Registry.

BACKGROUND: Tumors of the central nervous system (CNS) are the second most common type of pediatric cancer in Germany. We aimed to describe registration practice, incidence, and survival patterns for childhood CNS tumors in Germany for the past 40 years. PROCEDURE: Including all CNS tumor cases in children diagnosed at ages 0-14 years registered at the German Childhood Cancer Registry (GCCR) in 1980-2019 (for survival analysis 1980-2016), we calculated age-specific and age-standardized incidence rates (ASIR) over time, average annual percentage changes (AAPC), and 1- and 5-year overall survival. RESULTS: While we observed a pronounced increase in ASIR after the establishment of the GCCR during the 1980s, ASIR for all pediatric CNS tumors combined continued to increase markedly from 28.6 per million in 1990-1999 to 43.3 in 2010-2019 (AAPC = 2.7% in 1991-2010, AAPC = 0.3% in 2010-2019). The 5-year overall survival from CNS tumors improved from 63% in the 1980s, 70% in the 1990s to 79% in 2010-2016. These improvements have occurred across all age groups. Children diagnosed with ependymomas and choroid plexus tumors experienced the strongest increase (from 54% to 81%). CONCLUSIONS: Observed increases in incidence rates for pediatric CNS tumors are likely only partially caused by actual increasing case numbers. The majority is a function of improved registration and, to a minor extent, improvements in diagnostics. Survival from pediatric CNS tumors has, by and large, improved consistently, leading to a growing population of childhood cancer survivors with diverse health biographies and risk of lifelong adverse impact on health and wellbeing.

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas.

Gliomas constitute a diverse and complex array of tumors within the central nervous system (CNS), characterized by a wide range of prognostic outcomes and responses to therapeutic interventions. This literature review endeavors to conduct a thorough investigation of gliomas, with a particular emphasis on glioblastoma (GBM), beginning with their classification and epidemiological characteristics, evaluating their relative importance within the CNS tumor spectrum. We examine the immunological context of gliomas, unveiling the intricate immune environment and its ramifications for disease progression and therapeutic strategies. Moreover, we accentuate critical developments in understanding tumor behavior, focusing on recent research breakthroughs in treatment responses and the elucidation of cellular signaling pathways. Analyzing the most novel transcriptomic studies, we investigate the variations in gene expression patterns in glioma cells, assessing the prognostic and therapeutic implications of these genetic alterations. Furthermore, the role of epigenetic modifications in the pathogenesis of gliomas is underscored, suggesting that such changes are fundamental to tumor evolution and possible therapeutic advancements. In the end, this comparative oncological analysis situates GBM within the wider context of neoplasms, delineating both distinct and shared characteristics with other types of tumors.

Accuracy of MRI in Detecting 1p/19q Co-deletion Status of Gliomas: A Single-Center Retrospective Study.

Background Oligodendrogliomas, rare brain tumors in the frontal lobe's white matter, are reshaped by molecular markers like isocitrate dehydrogenase mutations and 1p/19q co-deletion, influencing treatment outcomes. Despite the initial indolence, these tumors pose a significant risk, with a median survival of 10-12 years. Non-invasive alternatives, such as magnetic resonance imaging (MRI) for assessing T2-fluid-attenuated inversion recovery (FLAIR) mismatch and calcifications, provide insights into molecular subtypes and aid prognosis. Our study explored these features to predict the oligodendroglioma status and refine patient management to improve outcomes. Methods In this retrospective study, patient data identified patients with suspected central nervous system tumors undergoing MRI, revealing low-grade gliomas. Surgical biopsy and 1p/19q fluorescence in situ hybridization confirmed the co-deletion status. MRI was used to assess various morphological features. Statistical analyses included x2 tests, Fisher's exact tests, Kruskal-Wallis tests, and binary logistic regression models, with significance set at p < 0.05. Results Seventy-three patients (median age, 37 years) were stratified according to 1p/19q co-deletion. Most (61.6%) were 18-40 years old and mostly male (67.1%). Co-deletion cases, primarily frontal lobe lesions (67.6%), were unilateral (88.2%), with 55.9% non-circumscribed margins and 58.8% ill-defined contours. Smooth contrast enhancement and no necrosis were observed in 48.1% of 1p/19q co-deletion cases. Logistic regression analysis showed a significant association between ill-defined/irregular contours and 1p/19q co-deletion. Fisher's exact test confirmed this but raised concerns about the small sample size influencing the conclusions. Conclusions This study established a significant link between glioma tumor contour characteristics, particularly irregular and ill-defined contours, and the likelihood of 1p/19q co-deletion. Our findings underscore the clinical relevance of using tumor contours in treatment decisions and prognosis assessments.

A system review of central nervous system tumors on children in China: epidemiology and clinical characteristics.

BACKGROUND: Central nervous system (CNS) tumors are the most common solid tumors in children and the leading cause of cancer-related death in the latter. Currently, the incidence rate exceeds that of leukemia and ranks first in the incidence of malignant tumors in children. METHODS: The epidemiological data on childhood CNS tumors were collected from the Chinese Cancer Registry Annual Report. The annual percent change (APC) of incidence and mortality-rate changes were estimated via Joinpoint regression. Due to a lack of pertinent data, we performed a system review on the clinical-pathological characteristics in Chinese publications. RESULTS: There was no significant increase in the incidence rate (APC: -0.1, 95% CI: -1.5 to 1.3), but there was a significant increase in the mortality rate (APC: 1.8, 95% CI: 0.3 to 3.4) for childhood CNS tumors. In the subgroup analysis, there were significant increases in both the incidence and mortality rates in rural areas (APC in the incidence: 6.2, 95% CI: 2.4 to 10.2; APC in mortality: 4.4, 95% CI: 0.4 to 8.4). The most common location and type of childhood CNS were, respectively, the cerebral hemisphere (25.5%, 95% CI: 21.7% to 29.4%) and astrocytomas (26.8%, 95% CI: 23.9% to 29.6%). CONCLUSIONS: The epidemiological trends, and the relevant prediction, highlighted the need to pay continual attention to childhood CNS tumors, and the clinicopathology evinced its own distinctive characteristics. Timely detection and effective treatment must be further promoted regarding childhood CNS tumors with a view to decreasing the disease burden, especially in rural areas.

Genetically modified ZIKA virus as a microRNA-sensitive oncolytic virus against central nervous system tumors.

Here we introduce a first-in-class microRNA-sensitive oncolytic Zika virus (ZIKV) for virotherapy application against central nervous system (CNS) tumors. The described methodology produced two synthetic modified ZIKV strains that are safe in normal cells, including neural stem cells, while preserving brain tropism and oncolytic effects in tumor cells. The microRNA-sensitive ZIKV introduces genetic modifications in two different virus sites: first, in the established 3'UTR region, and secondly, in the ZIKV protein coding sequence, demonstrating for the first time that the miRNA inhibition systems can be functional outside the UTR RNA sites. The total tumor remission in mice bearing human CNS tumors, including metastatic tumor growth, after intraventricular and systemic modified ZIKV administration, confirms the promise of this virotherapy as a novel agent against brain tumors-highly deadly diseases in urgent need of effective advanced therapies.

Proton MR spectroscopy shows improved performance to segregate high-grade astrocytoma subgroups when defined with the new 2021 World Health Organization classification of central nervous system tumors.

OBJECTIVES: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors prioritizes isocitrate dehydrogenase (IDH) mutation to define tumor types in diffuse gliomas, in contrast to the 2016 classification, which prioritized histological features. Our objective was to investigate the influence of this change in the performance of proton MR spectroscopy (1H-MRS) in segregating high-grade diffuse astrocytoma subgroups. METHODS: Patients with CNS WHO grade 3 and 4 diffuse astrocytoma, known IDH mutation status, and available 1H-MRS were retrospectively retrieved and divided into 4 groups based on IDH mutation status and histological grade. Differences in 1H-MRS between groups were analyzed with the Kruskal-Wallis test. The points on the spectrum that showed the greatest differences were chosen to evaluate the performance of 1H-MRS in discriminating between grades 3 and 4 tumors (WHO 2016 defined), and between IDH-mutant and IDH-wildtype tumors (WHO 2021). ROC curves were constructed with these points, and AUC values were calculated and compared. RESULTS: The study included 223 patients with high-grade diffuse astrocytoma. Discrimination between IDH-mutant and IDH-wildtype tumors showed higher AUC values (highest AUC short TE, 0.943; long TE, 0.864) and more noticeable visual differences than the discrimination between grade 3 and 4 tumors (short TE, 0.885; long TE, 0.838). CONCLUSION: Our findings suggest that 1H-MRS is more applicable to classify high-grade astrocytomas defined with the 2021 criteria. Improved metabolomic robustness and more homogeneous groups yielded better tumor type discrimination by 1H-MRS with the new criteria. CLINICAL RELEVANCE STATEMENT: The 2021 World Health Organization classification of brain tumors empowers molecular criteria to improve tumor characterization. This derives in greater segregation of high-grade diffuse astrocytoma subgroups by MR spectroscopy and warrants further development of brain tumor classification tools with spectroscopy. KEY POINTS: • The new 2021 updated World Health Organization classification of central nervous system tumors maximizes the role of molecular diagnosis in the classification of brain tumors. • Proton MR spectroscopy performs better to segregate high-grade astrocytoma subgroups when defined with the new criteria. • The study provides additional evidence of improved metabolic characterization of brain tumor subgroups with the new criteria.

Genetically modified ZIKA virus as a microRNA-sensitive oncolytic virus against central nervous system tumors

Here we introduce a first-in-class microRNA-sensitive oncolytic Zika virus (ZIKV) for virotherapy application against central nervous system (CNS) tumors. The described methodology produced two synthetic modified ZIKV strains that are safe in normal cells, including neural stem cells, while preserving brain tropism and oncolytic effects in tumor cells. The microRNA-sensitive ZIKV introduces genetic modifications in two different virus sites: first, in the established 3′UTR region, and secondly, in the ZIKV protein coding sequence, demonstrating for the first time that the miRNA inhibition systems can be functional outside the UTR RNA sites. The total tumor remission in mice bearing human CNS tumors, including metastatic tumor growth, after intraventricular and systemic modified ZIKV administration, confirms the promise of this virotherapy as a novel agent against brain tumors—highly deadly diseases in urgent need of effective advanced therapies.

Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors.

Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an "in-house" gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. This study represents the first comprehensive evaluation of germline variants in pediatric patients with CNS tumors in the Western Balkans region. Our results indicate the necessity of genomic research to reveal the genetic basis of pediatric CNS tumors, as well as to define targets for the application and development of innovative therapeutics that form the basis of the upcoming era of personalized medicine.

Targeted therapy for pediatric central nervous system tumors harboring mutagenic tropomyosin receptor kinases.

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.

Spinal Ependymomas: An Updated WHO Classification and a Narrative Review.

Ependymomas are neuroepithelial tumors that develop from ependymal cells found in the brain parenchyma and can spread to any part of the spinal cord. Three to six percent of all malignancies affecting the central nervous system (CNS) are ependymomas. Even the most talented surgeons are challenged by spinal cord ependymomas; as a result, research into this clinical phenomenon should continue. Since 1979, the World Health Organization (WHO) has published a classification and grading system for CNS malignancies to ensure consistent diagnostic standards worldwide. The WHO prepared an update on these tumors, paying particular attention to molecular techniques to categorize the therapeutic management of each patient with greater accuracy and clarity. We thoroughly reviewed the literature on the epidemiology, etiology, diagnosis, and treatment of spinal ependymomas since there has not been a recent review of these tumors. This included modifications to the 2021 WHO Classification of Tumors of the Central Nervous System.

Identifying brain tumor patients' subtypes based on pre-diagnostic history and clinical characteristics: a pilot hierarchical clustering and association analysis.

Introduction: Central nervous system (CNS) tumors are severe health conditions with increasing incidence in the last years. Different biological, environmental and clinical factors are thought to have an important role in their epidemiology, which however remains unclear. Objective: The aim of this pilot study was to identify CNS tumor patients' subtypes based on this information and to test associations with tumor malignancy. Methods: 90 patients with suspected diagnosis of CNS tumor were recruited by the Neurosurgery Unit of IRCCS Neuromed. Patients underwent anamnestic and clinical assessment, to ascertain known or suspected risk factors including lifestyle, socioeconomic, clinical and psychometric characteristics. We applied a hierarchical clustering analysis to these exposures to identify potential groups of patients with a similar risk pattern and tested whether these clusters associated with brain tumor malignancy. Results: Out of 67 patients with a confirmed CNS tumor diagnosis, we identified 28 non-malignant and 39 malignant tumor cases. These subtypes showed significant differences in terms of gender (with men more frequently presenting a diagnosis of cancer; p = 6.0 ×10-3) and yearly household income (with non-malignant tumor patients more frequently earning ≥25k Euros/year; p = 3.4×10-3). Cluster analysis revealed the presence of two clusters of patients: one (N=41) with more professionally active, educated, wealthier and healthier patients, and the other one with mostly retired and less healthy men, with a higher frequency of smokers, personal history of cardiovascular disease and cancer familiarity, a mostly sedentary lifestyle and generally lower income, education and cognitive performance. The former cluster showed a protective association with the malignancy of the disease, with a 74 (14-93) % reduction in the prevalent risk of CNS malignant tumors, compared to the other cluster (p=0.026). Discussion: These preliminary data suggest that patients' profiling through unsupervised machine learning approaches may somehow help predicting the risk of being affected by a malignant form. If confirmed by further analyses in larger independent cohorts, these findings may be useful to create potential intelligent ranking systems for treatment priority, overcoming the lack of histopathological information and molecular diagnosis of the tumor, which are typically not available until the time of surgery.