CNS Tumors Research Articles

Imaging of pediatric glioneuronal and neuronal tumors.

Glioneuronal tumors (GNTs) are an expanding group of primary CNS neoplasms, commonly affecting children, adolescents and young adults. Most GNTs are relatively indolent, low-grade, WHO grade I lesions. In the pediatric age group, GNTs have their epicenter in the cerebral cortex and present with seizures. Alterations in the mitogen-activated protein kinase (MAPK) pathway, which regulates cell growth, are implicated in tumorigenesis. Imaging not only plays a key role in the characterization and pre-surgical evaluation of GNTs but is also crucial role in follow-up, especially with the increasing use of targeted inhibitors and immunotherapies. In this chapter, we review the clinical and imaging perspectives of common pediatric GNTs.

Approaches to supratentorial brain tumours in children.

The differential diagnosis of supratentorial brain tumours in children can be challenging, especially considering the recent changes to the WHO classification of CNS tumours published in 2021. Many new tumour types have been proposed which frequently present in children and young adults and their imaging features are currently being described by the neuroradiology community.The purpose of this article is to provide guidance to residents and fellows new to the field of paediatric neuroradiology on how to evaluate an MRI of a patient with a newly diagnosed supratentorial tumour. Six different approaches are discussed including: 1. Tumour types, briefly discussing the main changes to the recent WHO classification of CNS tumours, 2. Patient age and its influence on incidence rates of specific tumour types, 3. Growth patterns, 4. Tumour location and how defining the correct location helps in narrowing down the differential diagnoses and 5. Imaging features of the tumour on DWI, SWI, FLAIR and post contrast sequences.

What Changed in CNS5? A Mini-Review on General Changes and Adult Diffuse Gliomas.

The fifth edition of the WHO classification of tumors of the central nervous system (WHO CNS5) was published in 2021 which is the sixth version of the international standard for the diagnostics of CNS tumors. Regular updates of the consortium to inform molecular and practical approaches to CNS tumor taxonomy (cIMPACT-NOW) shaped the WHO CNS5 which continues the trend of incorporating the molecular characteristics of tumors into the histological and immunohistochemical findings. The various updates can be classified into general changes across all tumors and specific changes within the tumor groups. This mini-review highlights the general changes and the major changes in adult diffuse gliomas.

Clinical features, MRI, molecular alternations, and prognosis of astrocytoma based on WHO 2021 classification of central nervous system tumors: A single-center retrospective study.

The diagnosis of glioma has advanced since the release of the WHO 2021 classification with more molecular alterations involved in the integrated diagnostic pathways. Our study aimed to present our experience with the clinical features and management of astrocytoma, IDH mutant based on the latest WHO classification. Patients diagnosed with astrocytoma, IDH-mutant based on the WHO 5th edition classification of CNS tumors at our center from January 2009 to January 2022 were included. Patients were divided into WHO 2-3 grade group and WHO 4 grade group. Integrate diagnoses were retrospectively confirmed according to WHO 2016 and 2021 classification. Clinical and MRI characteristics were reviewed, and survival analysis was performed. A total of 60 patients were enrolled. 21.67% (13/60) of all patients changed tumor grade from WHO 4th edition classification to WHO 5th edition. Of these, 21.43% (6/28) of grade II astrocytoma and 58.33% (7/12) of grade III astrocytoma according to WHO 4th edition classification changed to grade 4 according to WHO 5th edition classification. Sex (p = 0.042), recurrent glioma (p = 0.006), and Ki-67 index (p < 0.001) of pathological examination were statistically different in the WHO grade 2-3 group (n = 27) and WHO grade 4 group (n = 33). CDK6 (p = 0.004), FGFR2 (p = 0.003), and MYC (p = 0.004) alterations showed an enrichment in the WHO grade 4 group. Patients with higher grade showed shorter mOS (mOS = 75.9 m, 53.6 m, 26.4 m for grade 2, 3, and 4, respectively, p = 0.01). Patients diagnosed as WHO grade 4 according to the 5th edition WHO classification based on molecular alterations are more likely to have poorer prognosis. Therefore, treatment should be tailored to their individual needs. Further research is needed for the management of IDH-mutant astrocytoma is needed in the future.

Epidemiology of malignant gliomas in Iran: first report of Iranian National Population-based Cancer Registry, 2009-2017.

Malignant gliomas constitute the most common type of primary malignant brain tumors. Most previous studies have evaluated the epidemiology of malignant gliomas in developed countries. Hence, there is a lack of evidence in this regard from developing countries. This study is the first epidemiological report on the status of malignant glioma in Iran between 2009 and 2017. Data from the Iranian National Population-based Cancer Registry (covering 98% of the Iranian population) on CNS tumors recorded from 2009 to 2017 were used for analysis. Age-adjusted incidence rates were calculated by sex, tumor histology, tumor site, and year of diagnosis. Trend analysis of incidence rates was also performed. Survival data were recorded and the Cox proportional hazards model was used to evaluate underlying risk factors. A total of 8484 patients were diagnosed with malignant glioma between 2009 and 2017 in Iran. The overall age-adjusted incidence rate of malignant gliomas over the 9-year period was 1.71 per 100,000 persons. The most common histology of malignant gliomas was glioblastoma (81.4%). A significant increase in the incidence of malignant gliomas was found between 2009 and 2012. The median overall survival was 13.0 (95% CI 12.6-13.5) months over the study period. Older age groups, higher tumor grade, male sex, the first half of the study period, and receiving no treatment were significantly associated with worse prognoses. This study is the latest epidemiological report on the status of malignant gliomas in Iran. Although the overall incidence rate was lower than the rates in developed countries, several findings were consistent with those in prior reports.

FREQUENCY AND MORPHOLOGICAL PATTERNS OF CNS TUMORS IN A TERTIARY CARE HOSPITAL OF SOUTH PUNJAB

Background: The incidence of CNS tumours is increasing rapidly especially in young population. CNS tumours include a set of neoplasms which originate form brain parenchyma, pituitary gland, pineal gland, spinal cord and meninges. The aim of this study was to observe the frequency and morphological patterns of CNS tumours in a tertiary care hospital of South Punjab. Methods: A cross-sectional descriptive study of 100 cases of brain tumours was conducted at the Pathology Department of DG Khan Medical College, Dera Ghazi Khan. One-hundred cases of CNS tumour biopsies were included with the relevant clinical and radiological findings. Results: A total of 100 cases of CNS tumours were studied. The morphological distribution of various CNS tumours was as follows: Astrocytoma (49%), Meningioma (19%), Schwannoma (8%), Oligodandroglioma (6%), Metastatic tumour (4%), Ependymoma (4%), Pituitary Adenoma (2%), Medulloblastoma (2%), Mixed Gliomas (2%), Germ Cell Tumours (1%), Craniopharyngioma (1%), Lymphoma (1%), Vascular tumours (1%). Conclusion: Among the CNS tumours Astrocytomas were the commonest tumours followed by Meningiomas, Schwannoma and Oligodendroglioma. Pak J Pathol 2024;20(2):24-6

Prognostic significance of MRI contrast enhancement in newly diagnosed glioblastoma, IDH-wildtype according to WHO 2021 classification.

Contrast enhancement in glioblastoma, IDH-wildtype is common but not systematic. In the era of the WHO 2021 Classification of CNS Tumors, the prognostic impact of a contrast enhancement and the pattern of contrast enhancement is not clearly elucidated. We performed an observational, retrospective, single-centre cohort study at a tertiary neurosurgical oncology centre (January 2006 - December 2022). We screened adult patients with a newly-diagnosed glioblastoma, IDH-wildtype in order to assess the prognosis role of the contrast enhancement and the pattern of contrast enhancement. We included 1149 glioblastomas, IDH-wildtype: 26 (2.3%) had a no contrast enhancement, 45 (4.0%) had a faint and patchy contrast enhancement, 118 (10.5%) had a nodular contrast enhancement, and 960 (85.5%) had a ring-like contrast enhancement. Overall survival was longer in non-contrast enhanced glioblastomas (26.7 months) than in contrast enhanced glioblastomas (10.9 months) (p < 0.001). In contrast enhanced glioblastomas, a ring-like pattern was associated with shorter overall survival than in faint and patchy and nodular patterns (10.0 months versus 13.0 months, respectively) (p = 0.033). Whatever the presence of a contrast enhancement and the pattern of contrast enhancement, surgical resection was an independent predictor of longer overall survival, while age ≥ 70 years, preoperative KPS score < 70, tumour volume ≥ 30cm3, and postoperative residual contrast enhancement were independent predictors of shorter overall survival. A contrast enhancement is present in the majority (97.7%) of glioblastomas, IDH-wildtype and, regardless of the pattern, is associated with a shorter overall survival. The ring-like pattern of contrast enhancement is typical in glioblastomas, IDH-wildtype (85.5%) and remains an independent predictor of shorter overall survival compared to other patterns (faint and patchy and nodular).

Histopathologic and molecular profile of gliomas diagnosed in Lagos, Nigeria

Abstract Background The optimal diagnosis and management of patients with brain tumors currently uses the 2021 WHO integrated diagnosis of histomorphologic and molecular features. However, neuro-oncology practice in resource-limited settings usually relies solely on histomorphology. This study aimed to classify glioma cases diagnosed in the Department of Anatomic and Molecular Pathology, Lagos University Teaching Hospital, using the 2021 WHO CNS tumor classification. Methods Fifty-six brain tumors from 55 patients diagnosed with glioma between 2013 and 2021 were reevaluated for morphologic diagnosis. Molecular features were determined from formalin-fixed paraffin-embedded (FFPE) tissue using immunohistochemistry (IHC) for IDH1-R132H, ATRX, BRAF-V600E, p53, Ki67, and H3-K27M, OncoScan chromosomal microarray for copy number, targeted next generation sequencing for mutation and fusion and methylation array profiling. Results Of 55 central nervous system tumors, 3 were excluded from histomorphologic reevaluation for not being of glial or neuroepithelial origin. Of the remaining 52 patients, the median age was 20.5 years (range: 1 to 60 years), 38(73%) were males and 14(27%) were females. Seventy-one percent of the gliomas evaluated provided adequate DNA from archival FFPE tissue blocks. After applying the 2021 WHO diagnostic criteria the initial morphologic diagnosis changed for 35% (18/52) of cases. Diagnoses of 5 (9.6%) gliomas were upgraded, and 7 (14%) were downgraded. Conclusions This study shows that the incorporation of molecular testing can considerably improve brain tumor diagnoses in Nigeria. Furthermore, this study highlights the diagnostic challenges in resource-limited settings and what is at stake in the global disparities of brain tumor diagnosis.

MULTIDISCIPLINARY APPROACHES TO THE DIAGNOSIS AND TREATMENT OF CENTRAL NERVOUS SYSTEM TUMORS

The symptoms of CNS tumors vary according to the location and tumor neurobiology, the mass effect of the neoplasm increases intracranial pressure (ICP), favoring seizures, headaches, projectile vomiting, optic nerve edema, compression of cranial nerves pairs, among other manifestations, which can be confused with numerous differential diagnoses. The objective of this article is to review therapeutic, multidisciplinary approaches performed with patients diagnosed with CNS tumors on different continents over the last decades, contributing to more precise therapeutic decisions on the subject, whether through clinical or surgical approaches. This study is an integrative literature review, which searched through the DeCS/MeSH descriptors “Neurology,” “Neurosurgery,” “Central Nervous System Tumors,” “Treatment,” and “Diagnosis” on PubMed, ScienceDirect, and BVS databases. Multidisciplinary involvement is essential to improve surveillance and decision-making for patients with CNS tumors. Interactions between different healthcare areas are crucial for enhancing the diagnostic process and the treatment of patients with these tumors. Imaging technology proved to be extremely useful for the diagnosis and assessment of the patient’s preoperative course. In terms of tumor incidence analyzed, it is predominantly female, and the main age group ranges from 41 to 50 years, varying according to each patient’s individual situation. Meningioma was the most frequently observed diagnosis, encompassing neurosurgery as one of the widely used treatments for various types of CNS tumors. The average hospitalization period for patients varied from 8 to 25 days, depending on the needs and personal issues of each patient.

Pediatric brainstem glioma: a rare childhood cancer - clinical profile, treatment, and challenges of management - a single-center experience from a developing country

Introduction: Brainstem gliomas (BSGs) occur in the brainstem, located at the base of the brain. BSGs account for 10-20% of all primary CNS tumors. In a hospital-based study conducted at NICRH, BSGs constituted 7.69% of all childhood brain tumors. Objective: To determine the clinical profiles of childhood BSGs and assess the outcomes of pediatric BSGs while addressing the challenges of management. Methodology: It was a cross-sectional prospective study with a sample size of 44. We included all children during the study period and analyzed their data.The children were under 18 years of age. The study period was January 2020 and October 2022 at the Department of Pediatric Hematology and Oncology at the National Institute of Cancer Research and Hospital (NICRH), Bangladesh. Results: There were 44 patients, comprising 29 males and 15 females. The mean age of onset was 7 years. The majority (43.2%) of children fell within the 5-9 years age group. The most common symptoms were limb weakness, ataxia, and vision defects. The duration of symptoms varied from 10 days to 2 years. Sixteen of the patients experienced intracranial hypertension, which led to the development of hydrocephalus. The lesions were pontine in 18 cases, involving the entire brainstem in 13 cases, both pons and medulla in 7 cases, and medulla in 3 cases. Six patients underwent surgical intervention with histological evaluation, revealing astrocytoma (9.1%), oligodendroglioma (2.3%), and ependymoma (2.3%). Twenty-four (54.5%) patients received treatment, while others were unable to do so. The follow-up period extended to 12 months from the last enrollment. Only 8 patients completed both chemotherapy and radiotherapy treatments; other children discontinued or abandoned treatment due to financial constraints or the unavailability of 3D radiotherapy. Out of 44 children, a total of 41 patients passed away, with a mean survival period of 3.9 months. This is due to the high treatment cost in the private sector and disorganized government medical services for children with cancer. Conclusion: Most of the tumors in this series were located in the pons and demonstrated aggressive characteristics. The majority of our patients did not have access to radiotherapy due to their poor economic condition and the inadequate management of our government health system.

Incidence of venous thromboembolism and bleeding in patients with malignant central nervous system neoplasm: Systematic review and meta-analysis.

This systematic review and meta-analysis (PROSPERO CRD42023423949) were based on a standardized search of PubMed, Virtual Health Library and Cochrane (n = 1653) in July 2023. After duplicate removal, data screening and collection were conducted by independent reviewers. The combined rates and 95% confidence intervals for the incidence of VTE and bleeding were calculated using the random effects model with double arcsine transformation. Subgroup analyses were performed based on sex, age, income, and type of tumor. Heterogeneity was calculated using Cochran's Q test and I2 statistics. Egger's test and funnel graphs were used to assess publication bias. Only 36 studies were included, mainly retrospective cohorts (n = 30, 83.3%) from North America (n = 20). Most studies included were published in high-income countries. The sample size of studies varied between 34 and 21,384 adult patients, mostly based on gliomas (n = 30,045). For overall malignant primary CNS neoplasm, the pooled incidence was 13.68% (95%CI 9.79; 18.79) and 11.60% (95%CI 6.16; 18.41) for VTE and bleeding, respectively. The subgroup with elderly people aged 60 or over had the highest incidence of VTE (32.27% - 95%CI 14.40;53.31). The studies presented few biases, being mostly high quality. Despite some variability among the studies, we observed consistent results by performing sensitivity analysis, which highlight the robustness of our findings. Our study showed variability in the pooled incidence for both overall events and subgroup analyses. It was highlighted that individuals over 60 years old or diagnosed with GBM had a higher pooled incidence of VTE among those with overall CNS malignancies. It is important to note that the results of this meta-analysis refer mainly to studies carried out in high-income countries. This highlights the need for additional research in Latin America, and low- and middle-income countries.

A comprehensive evaluation of imaging features in pediatric spinal gliomas and their value in predicting tumor grade and histology

PurposePediatric spinal cord gliomas (PSGs) are rare in children and few reports detail their imaging features. We tested the association of tumoral grade with imaging features and proposed a novel approach to categorize post-contrast enhancement patterns in PSGs.MethodsThis single-center, retrospective study included patients <21 years of age with preoperative spinal MRI and confirmed pathological diagnosis of PSG from 2000-2022. Tumors were classified using the 5th edition of the WHO CNS Tumors Classification. Two radiologists reviewed multiple imaging features, and classified enhancement patterns using a novel approach. Fisher's exact test determined associations between imaging and histological features.ResultsForty-one PSGs were reviewed. Thirty-four were intramedullary, and seven were extramedullary. Pilocytic astrocytoma was the most common tumor (39.02%). Pain and weakness were the most prevalent symptoms. Seven patients (17.07%) died. Cyst, syringomyelia, and leptomeningeal enhancement were associated with tumor grade. Widening of the spinal canal was observed only in low-grade astrocytomas. There was a significant association between tumor grade and contrast enhancement pattern. Specifically, low-grade PSGs were more likely to exhibit type 1A enhancement (mass-like, with well-defined enhancing margins) and less likely to exhibit type 1B enhancement (mass-like, with ill-defined enhancing margins).ConclusionPSGs display overlapping imaging features, making grade differentiation challenging based solely on imaging. The correlation between tumor grade and contrast enhancement patterns suggests a potential diagnostic avenue, requiring further validation with larger, multicenter studies. Furthermore, Low-grade PSGs display cysts and syringomyelia more frequently, and leptomeningeal enhancement is less common.

METB-15. ROLE OF DNA METHYLATION PROFILING IN THE MANAGEMENT OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS: A SINGLE INSTITUTIONAL SERIES

Abstract BACKGROUND DNA methylation profiling has now been integrated into the WHO classification of CNS tumors and serves as confirmatory means to diagnose CNS tumors in conjunction with genetic sequencing/microarray analysis. The practical impact on patient care in the retrospective and prospective settings is less known. METHODS Methylation analysis was performed on a cohort of previously and newly diagnosed children with CNS tumors at Children’s Hospital Orange County from 2022-2023. Data regarding histologic diagnosis, integrated molecular diagnosis, methylation classification, timing of result completion and functional impact of methylation results on patient diagnosis/management was evaluated. RESULTS Forty patients (21 boys, ages 5 weeks-17 years) with previously diagnosed (N=11) or newly diagnosed (N=21) CNS tumors were evaluated by methylation analysis at one or more institutions. The most common tumor types were diffuse type pediatric high-grade glioma (N=6) and ependymoma PFA (n=4). Methylation analysis revealed no match in two cases (ALK-EML4 fusion embryonal tumor and recurrent low grade glioneuronal tumor) and had insufficient DNA extraction in one patient with low grade glioneuronal spinal cord tumor. Among the 5 tumors with duplicate methylation analyses at two institutions, three Ependymoma PFA subgroups were concordant while two showed differing classifications (diffuse type pediatric high-grade glioma RTK1 subtype vs. non- classifiable and medulloblastoma group 4 vs. non-WNT, non-SHH). In patients with previously diagnosed CNS tumors, methylation either led to a change in classification or modification of diagnosis in 7 out of 11 patients. The average time from surgery to the receipt of methylation results for newly diagnosed patients was 24 days (range 4-90 days). CONCLUSION Methylation analysis was beneficial in both the previously diagnosed and newly diagnosed setting in patients with previously difficult to classify tumors following conventional molecular analysis. Changes in tumor classification or modifications in diagnosis were observed in the majority of patients.

PATH-09. CNS EMBRYONAL TUMOUR WITHZNF532:NUTM1 FUSION: A RARE NEW CNS TUMOUR TYPE

Abstract BACKGROUND Rare embryonal and sarcomatous CNS tumours represent a diagnostic and therapeutic challenge. In the latest WHO 2021 several new tumour types, defined by molecular alterations, have been introduced. Some of these tumours have molecular counterparts outside the CNS e.g. CNS tumour with BCOR alteration or CIC-altered sarcoma.We report a CNS tumour with unusual histological and molecular features. METHODS/RESULTS A 3-year-old boy presented with a 5x3 cm sized tumour in the left lateral ventricle, which was removed at an external institution. After treatment with 1 cycle carboplatin/etoposide the patient presented at our clinic with leptomeningeal dissemination across all CNS compartments. Therapy was switched to HIT-MED Guidance augmented by intraventricular therapy. Histology showed a highly cellular tumour composed of small uniform cells with round nuclei, distinct nucleoli and a scant cytoplasm. The cells were arranged sheet-like without discernible background. Mitotic figures were conspicuous. Immunohistochemically, expression of Olig2, Chromogranin A, NCAM, BCOR and EGFR was present; synaptophysin and SOX10 were positive in a fraction of cells. DNA methylation profiling using the DKFZ and the Bethesda CNS tumour classifier did not match with any methylation class. Archer FUSIONPlex panel revealed a ZNF532::NUTM1 fusion, which was confirmed by RNA sequencing, leading to the diagnosis of a CNS embryonal tumour NEC with ZNF532::NUTM1 fusion. CONCLUSIONS NUTM1 fusion oncogenes, including among other fusion partners ZNF532, are drivers of aggressive NUT carcinomas. Furthermore, NUTM1 can be a fusion partner in CIC-rearranged sarcoma. The present case neither qualified as carcinoma nor sarcoma. As no clear response was evident after 3 cycles of HIT-MED Guidance therapy was switched to the Scandinavian Sarcoma Protocol. A similar case showing embryonal morphology has been recently reported (PMID 37203791). In conclusion, the spectrum of NUTM1-rearranged tumours is expanding and rare unclassifiable CNS embryonal tumours should be checked for NUTM1 immunopositivity/rearrangement.

TRLS-12. EFFICACY AND SAFETY OF ENTRECTINIB IN CHILDREN WITHNTRK ORROS1 FUSION-POSITIVE (FP) PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS

Abstract BACKGROUND Entrectinib (CNS-penetrant, TRK/ROS1 inhibitor) has shown efficacy and safety in children with NTRK/ROS1-fp CNS tumors. We present updated data from an integrated analysis of children with NTRK/ROS1-fp CNS tumors enrolled in three early-phase trials: STARTRK-NG (NCT02650401), TAPISTRY (NCT04589845) and STARTRK-2 (NCT02568267). METHODS TRK/ROS1 inhibitor-naïve patients &amp;lt;18 years old (YO) with NTRK/ROS1-fp CNS tumors with measurable/evaluable-only disease, who received ≥1 entrectinib dose before disease progression, unacceptable toxicity, or consent withdrawal, and with ≥6 months’ follow-up were efficacy evaluable. Any &amp;lt;18 YO on study who received ≥1 entrectinib dose, regardless of genetic alteration and follow-up duration, was evaluable for safety. Primary endpoint: blinded independent central review (BICR)-assessed confirmed objective response rate (ORR). Key secondary endpoints: BICR-assessed confirmed ORR in patients with measurable disease; duration of confirmed response (DoR); time to confirmed response (TtR); progression-free survival (PFS); safety. RESULTS On 16 July 2023 (cut-off for analysis), 27 patients were efficacy evaluable (NTRK-fp: n=20; ROS1-fp: n=7). Median age at enrolment: 4.0 Y (NTRK-fp) and 6.0 Y (ROS1-fp); 45.0% (NTRK-fp) and 42.9% (ROS1-fp) of patients received ≥2 prior therapy lines. Median survival follow-up: 26.2 months (NTRK-fp); 36.1 months (ROS1-fp). ORR: 50.0% (NTRK-fp) and 71.4% (ROS1-fp) in efficacy-evaluable patients, and 58.8% (n=10/17; NTRK-fp) and 83.3% (n=5/6; ROS1-fp) in patients with measurable disease. Median DoR: 25.4 months, TtR: 1.9 months, PFS: 23.1 months in NTRK-fp patients. DoR and PFS were not evaluable in ROS1-fp patients; median TtR was 1.9 months. In the safety-evaluable population (N=34), the most common adverse events were weight increase (50.0%), blood creatinine increase and anemia (each 41.2%). Bone fractures were reported in 26.5% of patients. Most fractures occurred in children 2–12 YO (n=7/9). CONCLUSIONS Our analysis confirms the rapid and durable activity of entrectinib in children with NTRK/ROS1-fp primary CNS tumors. The safety profile described was in line with previous reports.

LMIC-20. REAL-WORLD EXPERIENCE IN DEALING WITH CHILDREN WITH SUSPECTED CENTRAL NERVOUS SYSTEM (CNS) TUMORS AT THE CHILDREN’S HOSPITAL LAHORE (UCHS), PAKISTAN

Abstract BACKGROUND CNS tumors are the leading cause of cancer-related deaths in children in HICs, but data from LMICs are scarce. The objectives of this study were to document the trajectory of children with CNS tumors at a tertiary-care hospital in Pakistan. METHODS This prospective, analytic, cohort study recorded all new cases of suspected CNS tumors (birth to 16 years) presented from 2023/01/01 to 2023/12/31 at UCHS, Lahore. RESULTS A total of 145 cases were included. Median age at presentation was 7.0 years (1.5 months–15 years); male-to-female ratio was 1.4:1. Median time to presentation was 2 months (0.1 – 96 months); delay of &amp;gt;6 months was observed in 30.5% cases due to delayed presentation to medical facility (74%) and healthcare delay (26%). Headaches and vomiting (56%), focal neurological deficit (23%), and seizures (15%) were the most common presenting complaints. Consanguinity (46%), and family history of cancers (19%) were frequent; café au lait macules were observed in 9.7%. 50% tumors were infratentorial, 46% supratentorial and 4% spinal. Tumor excision was done in 45%, VP-shunts in 42%, and upfront chemotherapy in 2%. Only 60% had a final diagnosis. Tissue diagnosis in 39% cases showed Medulloblastoma (18 patients, 32%), Pilocytic Astrocytoma (27%), and High-grade glioma (16%) as the commonest diagnoses, while 21% had a radiological diagnosis based on CT/MRI features: DIPG/DMG (12%), Craniopharyngioma (7.6%), and Optic Pathway Glioma (1.4%). Of 18 medulloblastoma patients, only 7 received postoperative radiotherapy. Seventy (48%) patients expired (including 38 before surgery), 27% are on follow-up and 25% are LAMA/LTFU/defaulted treatment. One-year survival was 36% with median survival of 4 months (0.07-96 months). CONCLUSION Less than half of the patients with CNS tumors undergo active treatment, a large proportion leave treatment/follow-up and have poor overall survival. Considerable cases with cancer predisposition syndromes were suspected.

OTHR-29. A SINGLE INSTITUTION REVIEW REGARDING TRENDS IN THE MOLECULAR ANALYSIS OF PEDIATRIC CENTRAL NERVOUS SYSTEM (CNS) TUMORS AND GERMLINE ANALYSIS BETWEEN 2019 – 2023, EMPHASIZING THE IMPORTANCE OF EASY ACCESS TO COMPREHENSIVE TESTING

Abstract BACKGROUND Molecular characterization of pediatric CNS tumors improves diagnostic accuracy and guides treatment. Germline analysis is also important to uncover cancer predisposition syndromes, which influence the approach to treatment and tumor surveillance. The options for molecular assessment are influenced by availability, including access through a trial or insurance approval. METHODS A retrospective review of the molecular workup performed on all CNS tumors biopsied/resected at Children’s Minnesota from 2019 – 2023 was undertaken to look at trends in the specific tests performed over time and how the molecular results guided treatment. RESULTS Between 2019 – 2023, 220 patients at Children’s Minnesota were diagnosed with a CNS tumor. A total of 191 underwent surgery and 162 (85%) had sufficient tissue for molecular analysis. There was no apparent difference in the percentage of patients who underwent IHC/FISH/NGS between 2019 - 2023, but methylation profiling frequency increased over time (2019 2%, 2020 and 2021 10%, 2022 58% and 2023 71%). Frequency of germline analysis also increased (2019-2021 29%, 2022-52% and 2023-63%). Easy availability of comprehensive molecular and germline analysis for patients enrolled on COG-APEC14B1 is credited for these improving trends. Molecular analysis confirmed (59%) or supported (36%) the diagnosis, and guided treatment in 30% of cases (stratification of treatment in 89% of medulloblastoma and targeted treatment in 63% of high-grade glioma, 9% of medulloblastoma and 6% of low-grade glioma). Methylation profiling alone accurately diagnosed 79% of cases, including subtyping tumors. Germline analysis detected a pathogenic germline alteration in 14% of CNS tumor patients (NF1 5%; TP53 and BRIP1 1%; PALB1, NF2, TS2, SMARCB1, biallelic PMS2, CHEK2, FANCA, ORICH1 and SDHA 0.5%). CONCLUSION These findings demonstrate the importance of easy access to comprehensive molecular and germline analysis with quick turnaround time to provide the best diagnosis, prognosis and treatment options for pediatric CNS tumor patients.

RADT-11. PROTON BEAM THERAPY (PBT) FOR CENTRAL NERVOUS SYSTEM (CNS) TUMOURS IN CHILDREN: A CANADIAN PEDIATRIC BRAIN TUMOUR CONSORTIUM STUDY

Abstract BACKGROUND Radiotherapy is important for treating pediatric CNS tumours. The main modalities include photon therapy and PBT. PBT offers potential advantages over photon therapy in children since its precise dose control can limit long-term side effects. However, Canadian patients needing PBT are referred to the United States (US) because PBT is unavailable in Canada. We aimed to describe PBT use and outcomes over time for Canadian pediatric patients with CNS tumours. METHODS Patient demographics, treatment characteristics, and outcomes were extracted from medical records of patients from 10/13 Canadian provinces/territories. Patients diagnosed with a CNS tumour at ≤20 years old between 2001-2021 who received curative-intent PBT were included. PBT plans were compared using Fisher’s exact or Kruskal-Wallis rank sum tests. Overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS Of 195 patients (59.0% male) included in the study, majority were from Alberta (28.7%), Quebec (26.7%), British Columbia (22.6%), and Ontario (20.5%). Median age at diagnosis was 8.0 years. Most tumours (77.9%) were non-metastatic. Medulloblastoma was the most common diagnosis (30.8%). Provinces/territories referred patients to proton centres in the same geographical regions, except Alberta (74.5% referred to Florida). Referral numbers have increased ~180%/year since 2011. Median time from diagnosis to PBT was 126 days [11-5236] for all patients, and 36 days [21-1313] for medulloblastoma. Radiation doses, irradiation site, therapy duration, and time to treatment were not different (p≥0.2) across all PBT facilities for medulloblastoma. 5-year OS were 86.8% and 73.0% for the PBT study population and the Cancer in Young People-Canada reference population, respectively, in those aged &amp;lt;15 years. CONCLUSIONS Given the unavailability of PBT in Canada, pediatric CNS tumour patients were referred to US PBT facilities close in proximity. Further studies are needed to better understand provincial referral patterns and barriers to equitable PBT access across Canada.

METB-13. GERMLINE GENETIC TESTING IN CHILDREN WITH CNS TUMORS; FIRST-EVER EXPERIENCE FROM JORDAN

Abstract BACKGROUND It is expected that 10-15% of children with CNS tumors have an underlying cancer predisposition syndrome (CPS). This has important implications on treatment, cancer screening and family counseling. There is no published data on this genetic risk from Jordan. METHODS We retrospectively reviewed the medical charts of the Jordanian children &amp;lt;18 years old at the time of diagnosis with CNS tumors, and were treated at King Hussein Cancer Center/Jordan between January 2021 and December 2023. We reviewed their clinical characteristics and tumor diagnoses, then applied the updated Jongmans’ criteria and MIPOGG criteria and linked that with their germline genetic testing result if performed. RESULTS We identified 198 children (53% males); median age at diagnosis was 7years (range, 0-18 years). Consanguinity was found in 30% of families, and 35% had first/second degree relatives with cancer. Most common diagnoses were LGG (41%), HGG (22%) and medulloblastoma (14%). Most tumors were non-metastatic (90%) at initial diagnosis. Fifty-five percent of patients fulfilled the updated Jongmans’ criteria and 36% the MIPOGG criteria, however germline genetic testing was only performed for 34 patients (17%). Pathogenic germline variants were found in 15 patients (44%); 6 LGG (NF1 (3), TSC2, PTPN11, MUTYH), 4 medulloblastoma (SDHB, TP53, BRCA2, CHEK2), 4 HGG (MSH6 (3), TP53), and one had pathogenic NF2 gene. The presence of CPS affected the management received: children with NF1 were treated without tumor biopsy, the child with TSC2 received everolimus, and 3 children with MSH6 received checkpoint inhibitors instead of temozolomide. The underlying CPS also predicted prognosis e.g. rapid clinical deterioration in the TP53-mutated-SHH-medulloblastoma. Partial screening was provided to children with NF1, TSC, NF2, TP53 and BMMRD mutations. CONCLUSIONS High proportion of our patients fulfilled the criteria for referral to genetic clinic, but less than half were referred. Increasing awareness of these criteria is important. Identification of CPS impacted treatment and prognosis, yet families’ perceptions and attitudes toward these CPS need to be captured.

SURG-04. COMPARABLE SAFETY OF INTRATHECAL CHEMOTHERAPY GIVEN VIA LUMBAR PUNCTURE OR INTRAVENTRICULAR RESERVOIRS FOR PEDIATRIC CENTRAL NERVOUS SYSTEM (CNS) TUMORS: A SINGLE-INSTITUTION EXPERIENCE

Abstract BACKGROUND Intrathecal (IT) delivery of chemotherapy is utilized for the treatment of pediatric cancers, particularly leukemia and CNS tumors, either via lumbar puncture (LP) or intraventricular reservoir (IR). While the latter allows easier administration and more frequent IT dosing, data are lacking on the comparative safety and efficacy between these administration routes. We now present the IT chemotherapy experience from a single high-volume pediatric neuro-oncology center. METHODS We performed a retrospective chart review of patients with primary CNS tumors treated with IT chemotherapy between the years 2004-2022 at Dana-Farber/Boston Children’s Hospital. We collected demographic, clinical and outcome data. Safety evaluation included review of immediate (procedural) and short-term post-procedural assessments. RESULTS We identified 74 patients who received a total of 1,211 IT chemotherapy administrations. Excluding patients with insufficient data, we report on 38 patients who received 717 administrations (LP, n=207; IR, n=510). Median age was 26.5 months (range, 0.1-14.5), and diagnoses included medulloblastoma (n=14), ATRT (n=14) and others (n=10). Immediate events were reported in 11 (0.2%) IR and 1 (0.4%) LP administrations, i.e technical (n=5), high ICP (n=3), and immediate adverse side effects (n=3). Short-term events were reported in 16 (3%) IR and 12 (5.8%) LP administrations, i.e. fever (n=6), seizures (n=6), arachnoiditis (n=4), and others (n=10). No grade 4-5 adverse events were reported. No statistically significant difference was found between routes of administration and the rate of immediate or short-term events. Of note, 14/18 (78%) patients with CSF-positive disease achieved CSF clearance, with median time to response of 57 days (range, 27-446). CONCLUSIONS IT chemotherapy shows an excellent safety profile in children with malignant CNS tumors, with no differences between IR and LP administration. IT delivery can be efficacious in CFS clearance for patients with metastatic disease, lending support to inclusion of IT chemotherapy in current treatment regimens.