Central Nervous System Tumors in Adolescents and Young Adults.

Brain and central nervous system (CNS) tumors found in adolescents and young adults (AYA) are a distinct group of tumors that pose challenges not only to treatment but also to reporting. Overall, cancer that occurs in this age group is biologically distinct from those that occur in both younger and older age groups1,2 posing significant challenges for clinicians. The most commonly diagnosed histologies in AYA vary from those in both children age (0-14 years), and older adults (40+ years).3,4 Prognosis and expected survival also varies between younger and older adults, with those who are diagnosed with brain and CNS tumors at younger ages having significantly longer survival. Despite this survival advantage, recent analyses have reported that while cancer survival has been improving overall, AYA have not experienced these same increases in survival and in some cases may have worse survival than those cancers diagnosed in persons over age 40 years.5 This report provides an in depth analyses of the epidemiology of brain and CNS tumors in adolescents and young adults in the United States (US), and is the first report to provide histology-specific statistics in this population for both malignant and non-malignant brain and other CNS tumors. In 2006, the National Institutes of Health, the National Cancer Institute (NCI) and the LiveStrong Young Adult Alliance conducted a Progress Review Group to investigate AYA Oncology entitled Research and care imperatives for adolescents and young adults with cancer: A Report of the Adolescent and Young Adult Oncology Progress Review Group. This group established the standard age range for the AYA group as 15-39 years. This is the age range used by the Surveillance Epidemiology and End Results (SEER) program of the NCI, as well as in the 2015 CBTRUS Statistical Report.3,6 Brain tumors and other CNS tumors are less common in AYA than in older adults, but they have a higher incidence than brain tumors in children (age 0-14 years).3 Non-malignant tumors are significantly more common in AYA than children (Average annual age adjusted incidence in age 15-39 years: 6.17 per 100,000; age 0-14 years: 0.79 per 100,000), while malignant tumors are slightly more common in those age 0-14 years (Average annual age adjusted incidence in 15-39 years old: 3.26 per 100,000; 0-14 years old: 3.73 per 100,000). While a rare cancer overall, brain and CNS tumors are among the most common cancers occurring in this age group (4.4% of all cancers in those age 15-39 years as compared to 32.4% in children age 0-14 years, and 2.2% of cancers in adults age 40+ years).3,4,7 Malignant brain and CNS tumors are the 11th most common cancer and the 3rd most common cause of cancer death7,8 in the AYA population. Incidence rates of brain tumors overall as well as specific histologies vary significantly by age. It is, therefore, important to provide an accurate statistical assessment of brain and other CNS tumors in the adolescent and young adult population to better understand their impact on the US population and to serve as a reference for afflicted individuals, for researchers investigating new therapies and for clinicians treating patients.

Prior research shows that residential distance to a treatment facility may be an important factor in central nervous system (CNS) tumor outcomes. Our goal was to examine residential distance to the reporting hospital and overall survival in adolescents and young adults (AYA) diagnosed with CNS tumors. National Cancer Database data on AYA 15-39years old diagnosed with CNS and Other Intracranial and Intraspinal Neoplasms (CNS tumors) from 2010 to 2014 were obtained. Distance between the case's residence at diagnosis or initial treatment and the reporting hospital was classified in miles as short (≤ 12.5), intermediate (> 12.5 and < 50), and long (≥ 50). Cox proportional hazards regression models were used for analyses. Among 9335 AYA diagnosed with CNS tumors, hazard ratios (HRs) were 1.06 (95% CI 0.96-1.17) and 0.82 (95% CI 0.73-0.93) for those with residences at intermediate and long vs. short distances, respectively, after adjusting for age, sex, race/ethnicity, and zip-code level education and income. After adjusting for the facility volume of CNS tumor patients, the association was attenuated for long vs. short distance residences (HR 0.92, 95% CI 0.81-1.04). The HRs varied by tumor type, race/ethnicity, and zip-code level income with significantly lower hazards of death for those with residences at long vs. short distances for low-grade astrocytic tumors, ependymomas, non-Hispanic Whites, and those from higher-income areas. Living at long distances for CNS tumor care may be associated with better survival in AYA patients. This may be explained by travel to facilities with more experience treating CNS tumors.

Purpose: In recent decades, the survival outcomes among adolescent and young adults (AYAs, 15-39 years) have not improved substantially, especially among AYAs with primary central nervous system (CNS) tumors. While this is likely multifactorial, low participation in clinical trials among AYAs is thought to be a critical contributing factor. In this study, we describe the pattern of clinical trial enrollment among AYAs with primary CNS tumors at our institution. Methods: We performed a retrospective, IRB-approved chart review of AYAs with CNS tumors treated at the Dana-Farber Cancer Institute (DFCI) between January 2009 and December 2018. We used logistic regression analyses and descriptive statistics to analyze this sample and determine the clinical trial enrollment at the pediatric affiliate (Dana-Farber/Boston Children's Cancer and Blood Disorders Center) and adult affiliate (Dana-Farber/Brigham and Women's Cancer Center). Results: Ninety-three AYA patients with primary CNS tumors were treated at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, while 507 patients with primary CNS gliomas were treated at the Dana-Farber/Brigham and Women's Cancer Center. At the pediatric affiliate, 35.4% (33/93) of AYAs were enrolled in a therapeutic clinical trial, while at the adult affiliate, 15.8% (80/507) of AYAs were enrolled in a clinical trial. High-grade gliomas were associated with significantly higher rates of enrollment in the adult affiliate. Conclusions: Clinical trial enrollment remains poor among AYAs with CNS tumors, and clinical trial enrollment participation is modestly higher in the pediatric setting. Our study demonstrates the continued need to evaluate and address factors associated with clinical trial enrollment among AYAs with CNS tumors.

BackgroundLittle aetiological epidemiological research has been undertaken for major cancers occurring in teenagers and young adults (TYA). Population mixing, as a possible proxy for infectious exposure, has been well researched for childhood malignancies. We aimed to investigate effects of population mixing in this older age group using an English national cancer dataset.MethodsCases of leukaemia, lymphoma and central nervous system (CNS) tumours amongst 15–24 year olds in England (diagnosed 1996–2005) were included in the study. Data were obtained by ward of diagnosis and linked to 1991 census variables including population mixing (Shannon index); data on person-weighted population density and deprivation (Townsend score) were also used and considered as explanatory variables. Associations between TYA cancer incidence and census variables were investigated using negative binomial regression, and results presented as incidence rate ratios (IRR) with 95% confidence intervals (CI).ResultsA total of 6251 cases of leukaemia (21%), lymphoma (49%) and CNS tumours (30%) were analysed. Higher levels of population mixing were associated with a significant decrease in the incidence of CNS tumours (IRR = 0.83, 95% CI = 0.75-0.91), accounted for by astrocytomas and ‘other CNS tumours’; however, there was no association with leukaemia or lymphoma. Incidence of CNS tumours and lymphoma was 3% lower in more deprived areas (IRR = 0.97, 95% CI = 0.96-0.99 and IRR = 0.97, 95% CI =0.96-0.98 respectively). Population density was not associated with the incidence of leukaemia, lymphoma or CNS tumours.ConclusionsOur results suggest a possible role for environmental risk factors with population correlates in the aetiology of CNS tumours amongst TYAs. Unlike studies of childhood cancer, associations between population mixing and the incidence of leukaemia and lymphoma were not observed.

Purpose: While central nervous system (CNS) tumors account for only 10% of adolescent and young adult (AYA) cancers, they are the leading cause of cancer death in this age group. Using national data for Australia, we describe the presentation, treatment, and survival for AYAs diagnosed with CNS tumors. Methods: A population-based study of 15-24 year-olds diagnosed with CNS tumors (low- and high-grade glioma [LGG, HGG], medulloblastoma [MB], primitive neuroectodermal tumors [PNET], ependymoma [EP]) or other (e.g., low-grade neuronal tumor) between 2007 and 2012. Clinical details were extracted from hospital medical records for each patient. Treatment centers were classified as pediatric or adult services. Results: Two hundred seventy-five patients (129 LGG, 77 HGG, 23 MB, 10 PNET, 19 EP, 17 other) were identified, with 17% treated at pediatric hospitals. Symptoms (headache [53%], nausea [31%]) were present for a median of 3 weeks before consulting a health professional. Of LGG patients, 15% had radiotherapy (RT) and 12% chemotherapy (CT). Of HGG patients, 81% had RT and 75% CT. All MB and PNET were managed with surgery, and 74% of MB and 80% of PNET had both RT and CT. Treatment did not differ by treatment center type. Five-year survival for LGG and EP was over 80%, but was 42% for HGG and 20% for PNET. Conclusions: This national, population-based study indicates similar treatment for AYA patients with CNS tumors between pediatric and adult services. Poor outcomes for HGG and PNET patients highlight the need for clinical trials of novel approaches for these tumors.

Central nervous system (CNS) tumors rank among the top 5 cancers diagnosed in young adults aged 20 to 39 years at diagnosis and show a clear male excess in incidence. It is unknown whether sex differences in survival persist across histologic types and depend on the treatment received. From the National Cancer Database (2004-2016), young adults (aged 20-39 years) who had been diagnosed with CNS tumors were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated as measures of association between sex and death via Cox regression. An inverse odds weighting mediation analysis was performed with treatment received as a mediator. There were 47,560 cases (47% male). Males had worse overall survival than females for 9 of 16 histologic types, including diffuse astrocytoma, glioblastoma, and meningioma (all P < .05). Males had an increased risk of death after a brain tumor diagnosis overall (HR, 1.47; 95% CI, 1.41-1.53) and for 8 histologies. There was a significant association between male sex and death overall that was mediated by treatment received (indirect-effect HR, 1.17; 95% CI, 1.15-1.18), but no single histology had a significant indirect effect. All histologies examined in mediation analyses had significant direct effects for sex. The excess mortality due to sex was 20% for all CNS tumors combined and 34% among males with CNS tumors. Overall, treatment received may mediate a portion of the association between sex and death after a CNS tumor, but sex itself appears to be a stronger risk factor for death in this study.

Medicaid enrollment has been associated with disparities in younger cancer patient survival. To further understand this association for central nervous system (CNS) tumor patients, we used Surveillance, Epidemiology, and End Results (SEER)-Medicaid-linked data to examine associations between Medicaid enrollment and enrollment timing and (1) diagnosis stage, and (2) CNS tumor death. Individuals diagnosed with a first malignant primary CNS tumor between 0 and 39 years from 2006 to 2013 were included. Medicaid enrollment was first classified as enrolled versus not enrolled with those enrolled further classified as having continuous, discontinuous (at diagnosis or other discontinuous), or other enrollment. We used logistic and Cox Proportional Hazards regression stratified by age to calculate adjusted odds ratios (ORs) and hazard ratios (HRs) for those 0-14 and 15-39 years. Among 10 107 CNS tumor patients, we found significantly higher odds of regional/distant versus in situ/localized stage diagnoses for those with other discontinuous (OR0-14 = 1.50, 95% CI: 1.15-1.95) and at diagnosis (OR15-39 = 1.41, 95% CI: 1.11-1.78) Medicaid enrollment versus those not enrolled. Those enrolled versus not enrolled in Medicaid had a higher hazard of CNS tumor death for both age groups (HR0-14 = 1.60 95% CI: 1.37-1.86; HR15-39 = 1.50, 95% CI: 1.39-1.62) with the highest hazards for those enrolled at diagnosis (HR0-14 = 1.83, 95% CI: 1.51-2.22; HR15-39 = 1.93, 95% CI: 1.77-2.10). Medicaid enrollment is associated with a higher risk of CNS tumor death with an almost 2-fold higher risk for young CNS tumor patients enrolled at diagnosis. These results support the critical need for consistent health insurance coverage for young CNS tumor patients.

Pediatric central nervous system (CNS) tumors are the most common solid cancers and the leading cause of cancer-related morbidity and mortality in children. The global demographic and epidemiological trends indicate a significant increase in childhood and adolescent cancers, including pediatric brain tumors, in low- and middle-income countries, particularly in Sub-Saharan African countries necessitating the dire need of multidisciplinary Pediatric Neuro-Oncology (PNO) teams to improve outcomes. The primary objective of the study was to evaluate the patterns, clinical presentations, time to diagnosis (TD), and treatment provided to pediatric and adolescent patients with central nervous system tumors who were discussed at the pediatric neuro-oncology tumor board and treated by the neuro-oncology team at Tikur Anbessa Specialized Hospital in Ethiopia. This retrospective cross-sectional study was conducted in the Pediatric Hematology and Oncology (PHO) unit at Tikur Anbessa Specialized Hospital in Ethiopia. It included all pediatric patients under 15 years old with primary central nervous system (CNS) tumors from December 2021 to May 2024. The study aimed to provide an overview of the sociodemographic characteristics of the children, clinical presentation, time to diagnosis, histopathology of the tumors, and treatment modalities recommended by the PNO tumor board. A total of two hundred ten patients with pediatric CNS tumors were discussed and reviewed at the Pediatric Neuro-Oncology (PNO) Tumor Board during the study period. More than half of the patients (54.8%, n = 114) were males. The median age at diagnosis was 7 years, and nearly half of the patients (48.6%) were between 5 and 10 years old. The most common clinical presentations were headache (66.2%), vomiting (64.3%), visual symptoms (44.8%), and cerebellar symptoms (43.8%). The median time to diagnosis was 90 days (IQR 60-210), and 60% of the patients presented after three months of symptom onset of the disease. The most common pediatric CNS tumors were medulloblastoma and embryonal CNS tumors, accounting for 32.9% (n = 69), followed by astrocytic tumors; 30.0% (n = 63), craniopharyngiomas (14.0%), and ependymal tumors (11.4%). The main treatments offered by the PNO Tumor Board were a combination of surgery, radiotherapy, and systemic chemotherapy (33.8%), surgery alone (23.8%), and surgery with radiotherapy (21.4%). The PNO Tumor Board was primarily attended by pediatric hematology-oncology fellows, pediatric oncologists (90%), and neurosurgeons (86%). This study focused on analyzing the age distribution, clinical presentation, time to diagnosis, burden, and patterns of pediatric primary CNS tumors at the largest tertiary referral center in Ethiopia. It is imperative to prioritize educating healthcare professionals about the symptoms and signs of CNS tumors in children, promoting early diagnosis, facilitating timely referrals, and enhancing the effectiveness of the PNO tumor board. These measures should be considered essential aspects of care for children with CNS tumors.

Introduction: Central Nervous System (CNS) tumours are a common cause of cancer-related deaths in adolescents and young adults. The challenges in diagnosing and treating CNS tumours in this age group are unique and require special attention. Aim: To study the histopathological spectrum of CNS tumours in Adolescents and Young Adults (AYA). Materials and Methods: Present five-year cross-sectional study was conducted on CNS biopsies received in the Department of Pathology at Dayanand Medical College and Hospital, Ludhiana, Punjab, India, from July 1, 2016, to June 30, 2021, to analyse the histopathological spectrum of CNS tumours in the AYA group based on the site of the lesion, age, gender, and Isocitrate Dehydrogenase (IDH) status. Results: During the study period, a total of 215 cases of CNS tumours were identified, of which 52 (24.2%) belonged to the AYA group. Of these, 35 (67.3%) were males and 17 (32.7%) were females. The majority of the patients presented with complaints of headache (50/52, 96.1%), with the frontal lobe being the most common site of involvement (21/52, 40.4%). Diffuse astrocytic and oligodendroglial tumours were the most commonly observed (23/52, 44.2%). Conclusion: CNS tumours are one of the most common cancer diagnosis among the AYA group, and awareness should be enhanced among histopathologists and oncologists regarding these tumours based on the updated classification.

Central nervous system (CNS) tumors originate from the spinal cord or brain. The study showed that even with aggressive treatment, malignant CNS tumors have high mortality rates. However, CNS tumor risk factors and molecular mechanisms have not been verified. Due to the reasons mentioned above, diagnosis and treatment of CNS tumors in clinical practice are currently fraught with difficulties. Circular RNAs (circRNAs), single-stranded ncRNAs with covalently closed continuous structures, are essential to CNS tumor development. Growing evidence has proved the numeral critical biological functions of circRNAs for disease progression: sponging to miRNAs, regulating gene transcription and splicing, interacting with proteins, encoding proteins/peptides, and expressing in exosomes. This review aims to summarize current progress regarding the molecular mechanism of circRNA in CNS tumors and to explore the possibilities of clinical application based on circRNA in CNS tumors. We have summarized studies of circRNA in CNS tumors in Pubmed. This review summarized their connection with CNS tumors and their functions, biogenesis, and biological properties. Furthermore, we introduced current advances in clinical RNA-related technologies. Then we discussed the diagnostic and therapeutic potential (especially for immunotherapy, chemotherapy, and radiotherapy) of circRNA in CNS tumors in the context of the recent advanced research and application of RNA in clinics. CircRNA are increasingly proven to participate in decveloping CNS tumors. An in-depth study of the causal mechanisms of circRNAs in CNS tomor progression will ultimately advance their implementation in the clinic and developing new strategies for preventing and treating CNS tumors.

BackgroundWe aimed to examine evidence for an infectious aetiology among teenagers and young adults (TYA) by analysing monthly seasonality of diagnosis and birth amongst 15–24 year olds diagnosed with cancer in England.MethodsCases of leukaemia, lymphoma and central nervous system (CNS) tumours were derived from the national TYA cancer register (1996–2005). Incidence rates (IR) and trends were assessed using Poisson regression. Seasonality of diagnosis and birth was assessed using Poisson and logistic regression respectively with cosine functions of varying periods.ResultsThere were 6251 cases diagnosed with leukaemia (n = 1299), lymphoma (n = 3070) and CNS tumours (n = 1882), the overall IR was 92 (95% CI 89–96) per 1,000,000 15–24 year olds per year.There was significant evidence of seasonality around the time of diagnosis for Hodgkin’s lymphoma (P < 0.001) with a peak in February, and for ‘other CNS tumours’ (P = 0.010) with peaks in December and June. Birth peaks for those with ‘other Gliomas’ (Gliomas other than Astrocytoma and Ependymoma) were observed in May and November (P = 0.015).ConclusionOur novel findings support an infectious aetiological hypothesis for certain subgroups of TYA cancer in England. Further work will examine correlation with specific infections occurring around the time of birth and diagnosis within certain diagnostic groups.

Brain tumors account for the majority of cancer-related deaths in adolescents and young adults (AYAs), defined as individuals aged 15 to 39. AYAs constitute a distinct population in which both pediatric- and adult-type central nervous system (CNS) tumors can be observed. Clinical manifestations vary depending on tumor location and often include headaches, seizures, focal neurological deficits, and signs of increased intracranial pressure. With the publication of the updated World Health Organization CNS tumor classification in 2021, diagnoses have been redefined to emphasize key molecular alterations. Gliomas represent the majority of malignant brain tumors in this age group. Glioneuronal and neuronal tumors are associated with longstanding refractory epilepsy. The classification of ependymomas and medulloblastomas has been refined, enabling better identification of low-risk tumors that could benefit from treatment de-escalation strategies. Owing to their midline location, germ cell tumors often present with oculomotor and visual alterations as well as endocrinopathies. The management of CNS tumors in AYA is often extrapolated from pediatric and adult guidelines, and generally consists of a combination of surgical resection, radiation therapy, and systemic therapy. Ongoing research is investigating multiple agents targeting molecular alterations, including isocitrate dehydrogenase inhibitors, SHH pathway inhibitors, and BRAF inhibitors. AYA patients with CNS tumors should be managed by multidisciplinary teams and counselled regarding fertility preservation, psychosocial comorbidities, and risks of long-term comorbidities. There is a need for further efforts to design clinical trials targeting CNS tumors in the AYA population.

In the World Health Organization tumor classification (fifth edition), central nervous system (CNS) tumors with BCOR internal tandem duplications have been recognized as a new tumor type. Some recent studies have reported CNS tumors with EP300::BCOR fusions, predominantly in children and young adults, expanding the spectrum of BCOR-altered CNS tumors. This study reports a new case of high-grade neuroepithelial tumor (HGNET) with an EP300::BCOR fusion in the occipital lobe of a 32-year-old female. The tumor displayed anaplastic ependymoma-like morphologies characterized by a relatively well-circumscribed solid growth with perivascular pseudorosettes and branching capillaries. Immunohistochemically, OLIG2 was focally positive and BCOR was negative. RNA sequencing revealed an EP300::BCOR fusion. The Deutsches Krebsforschungszentrum DNA methylation classifier (v12.5) classified the tumor as CNS tumor with BCOR/BCORL1 fusion. The t-distributed stochastic neighbor embedding analysis plotted the tumor close to the HGNET with BCOR alteration reference samples. BCOR/BCORL1-altered tumors should be included in the differential diagnosis of supratentorial CNS tumors with ependymoma-like histological features, especially when they lack ZFTA fusion or express OLIG2 even in the absence of BCOR expression. Analysis of published CNS tumors with BCOR/BCORL1 fusions revealed partly overlapping but not identical phenotypes. Further studies of additional cases are required to establish their classification.

Dr. Penn would be pleased to note that the stated United Network for Organ Sharing (UNOS) interpretation of Scientific Registry of Transplant Recipients (SRTR) data on the risk of donor central nervous system (CNS) tumor transmission is identical to his initial opinion published in 1991 (1–4). The manner in which the overall risk of tumor transmission is reported deserves comment. Data regarding the risk of CNS tumor transmission is only relevant when expressed as the following proportion: the number of transplant recipients who experience donor CNS tumor transmission out of the entire population of transplant recipients who receive organs from donors with CNS tumors. Expression of this risk using other denominators (such as all solid-organ donors) can be misleading because the overwhelming majority of the population is not at risk for donor-related CNS tumor transmission. UNOS presentation of data in this manner only means one thing: that donors with a history of CNS tumors are relatively infrequent, and the risk of transmission of a CNS tumor in most patients with CNS tumors is also infrequent. UNOS publications have generally held that the risk of tumor transmission in transplant recipients is small. It is small however, because of two reasons. First, donors with CNS tumors are very infrequent. Second, among donors with CNS tumors, those that are high risk for transmission actually represent a minority of this group of donors. The transplant community must be sophisticated enough, however, to understand that a high-risk population does exist and that great care should be used to identify these donors and avoid use of their organs. When this level of sophistication does not exist, the risk of tumor transmission will be real. Definition of risk factors for tumor transmission requires a critical mass of recipients experiencing these events. For relatively rare events, event-based registries have substantial advantages over mandatory reporting registries, where capture rates are always at issue. The Israel Penn International Transplant Tumor Registry (IPITTR) has the only data set capable of defining risk factors for tumor transmission because it has a substantial number of recipients with donor CNS tumor transmission. In contrast, the paucity of observed donor CNS tumor transmission events in the Australian New Zealand and SRTR registries precludes such analyses. Furthermore, IPITTR collects substantially more detailed information, including pathology reports, and therefore data collected on individual events is substantially more robust. Mandatory reporting registries simply cannot require such detailed reporting from all centers. This issue, more than any other, highlights the importance of both types of registries in answering questions regarding infrequent events such as donor-related CNS tumor transmission. The importance of defining risk factors for donor CNS tumor transmission arises when a transplant team is under time pressure to make a decision about using organs from a donor with a history of CNS tumor. The IPITTR is consulted relatively frequently on these issues, and the purpose of our ongoing work on this issue is to better define those donors with a history of CNS tumors who represent the highest risk of tumor transmission so we can better advise the transplant community in a consultative setting. The IPITTR is continuing to collect highly detailed data on patients in the United States and the international transplant community on patients receiving organs from donors with a history of CNS tumors to better define those donors at highest risk of tumor transmission. Ongoing updates of these data with scientific publication will improve the consultative services on these donors to the international transplant community. Joseph F. Buell Thomas M. Beebe Thomas G. Gross Jennifer Trofe Michael J. Hanaway Rita R. Alloway M. Roy First E. Steve Woodle FACS, The Israel Penn International Transplant Tumor Registry The University of Cincinnati Cincinnati, OH

BackgroundRecent large-scale genomic studies have revealed a spectrum of genetic variants associated with specific subtypes of central nervous system (CNS) tumors. The aim of this study was to determine the clinical utility of comprehensive genomic profiling of pediatric, adolescent and young adult (AYA) CNS tumors in a prospective setting, including detection of DNA sequence variants, gene fusions, copy number alterations (CNAs), and loss of heterozygosity.MethodsOncoKids, a comprehensive DNA- and RNA-based next-generation sequencing (NGS) panel, in conjunction with chromosomal microarray analysis (CMA) was employed to detect diagnostic, prognostic, and therapeutic markers. NGS was performed on 222 specimens from 212 patients. Clinical CMA data were analyzed in parallel for 66% (146/222) of cases.ResultsNGS demonstrated clinically significant alterations in 66% (147/222) of cases. Diagnostic markers were identified in 62% (138/222) of cases. Prognostic information and targetable genomic alterations were identified in 22% (49/222) and 18% (41/222) of cases, respectively. Diagnostic or prognostic CNAs were revealed by CMA in 69% (101/146) of cases. Importantly, clinically significant CNAs were detected in 57% (34/60) of cases with noncontributory NGS results. Germline cancer predisposition testing was indicated for 27% (57/212) of patients. Follow-up germline testing was performed for 20 patients which confirmed a germline pathogenic/likely pathogenic variant in 9 cases: TP53 (2), NF1 (2), SMARCB1 (1), NF2 (1), MSH6 (1), PMS2 (1), and a patient with 47,XXY Klinefelter syndrome.ConclusionsOur results demonstrate the significant clinical utility of integrating genomic profiling into routine clinical testing for pediatric and AYA patients with CNS tumors.