Brain Tumours in Individuals with Down Syndrome: An Individual Patient Data Meta-analysis of Incidence, Patterns and Outcomes

Brain Tumours in Individuals with Down Syndrome: An Individual Patient Data Meta-analysis of Incidence, Patterns and Outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Brain Tumours in Individuals with Down Syndrome: An Individual Patient Data Meta-analysis of Incidence, Patterns and Outcomes Yasser F Almealawy, Jeremiah Hilkiah Wijaya, Danisha Kumar, Mohammed Q. Alibraheemi, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8168623/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Brain tumours in individuals with Down syndrome (DS) are extremely rare, and little is known about their types, locations, molecular features, or outcomes. While DS is associated with a high risk of leukemia, solid tumours—including those of the central nervous system—appear unusually uncommon. Methods We performed a systematic review and individual patient data meta-analysis of published cases of brain tumours in DS, following PRISMA guidelines. Searches of PubMed, Scopus, and Web of Science up to 2025 identified studies reporting clinical, histological, treatment, or outcome data. Data on demographics, tumour characteristics, molecular markers, therapies, and survival were extracted and analyzed using descriptive statistics, survival analysis, and risk modeling. Results Among 41 patients (mean age 13.6 years), most were pediatric (70.7%) and male (85.4%). Germ cell tumors predominated (46.3%), mainly in the basal ganglia/thalamus and pineal regions. All informative molecular tests confirmed trisomy 21 with diverse secondary alterations but no recurrent “second hit.” Intraventricular and pineal tumors showed significantly higher mortality risk (p < 0.001), while germ cell (HR 0.09, p < 0.001) and glial tumors (HR 0.22, p = 0.022) were associated with better outcomes. SALL4 (HR 16.9, p = 0.013) and GFAP positivity (HR 5.3, p = 0.039) predicted worse survival. Recurrence increased mortality risk (HR 2.98, p = 0.044). Overall survival plateaued above 50% at 5 years, with no median survival reached. Conclusions Brain tumours in DS show a distinct pattern, clustering in deep and midline structures and dominated by germ cell tumours, medulloblastomas, and high-grade gliomas. Outcomes depend primarily on tumour location and type rather than underlying comorbidities. These findings emphasize the need for careful, tailored management and highlight the importance of collaborative studies to improve understanding and treatment strategies in this vulnerable population. Down Syndrome Brain neoplasms Trisomy 21 Survival outcomes Mortality Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Brain tumours in individuals with Down syndrome (DS) sit at the intersection of a common genetic condition and a highly unusual cancer risk profile. DS affects roughly 1 in 700 live births and is the most frequent chromosomal abnormality worldwide 1 . As survival has improved into middle and older adulthood, cancer has become a key contributor to morbidity and mortality in this population. Epidemiologic studies consistently show a 10–20-fold increased risk of acute leukaemias, contrasted with an approximately twofold lower risk of solid tumours compared with the general population, and a 50–100-fold lower likelihood of dying from a solid tissue cancer 2 . Within this solid-tumour deficit, brain tumours appear particularly rare, with only small registry series and scattered case reports suggesting that central nervous system (CNS) neoplasms represent a very small fraction of cancers in DS and that their true incidence, spectrum, and outcomes remain poorly defined 3 . The distinctive tumour pattern in DS is thought to reflect the dosage effect of triplicated chromosome 21 genes, which alters developmental biology, immune function, and oncogenic signalling. Several chromosome 21–encoded proteins, including DYRK1A 4 and RCAN1 (DSCR1), inhibit the calcineurin–NFAT pathway and angiogenesis, and are proposed to confer systemic protection against many solid tumours. Additional mechanisms such as overexpression of candidate tumour suppressors (e.g. ETS2) 5 , disturbed metabolism, increased apoptosis, and impaired neo-angiogenesis may further lower solid-tumour risk in DS. However, CNS tumour biology in DS is unlikely to be uniformly protective. Multi-institutional data indicate that primary CNS germ cell tumours (GCTs) are the most common CNS neoplasms in DS, and that DS and other chromosomal sex aneuploidies are over-represented among patients with intracranial GCTs 6 ; medulloblastoma and other embryonal or glial tumours, while rare, are increasingly reported. These observations suggest that trisomy 21 may differentially modulate specific neurodevelopmental lineages and signalling pathways (e.g. SHH, WNT, MYC) rather than conferring uniform protection across all brain tumour types. Despite these clinical and biological implications, data on brain tumours in DS remain fragmented, limited to isolated case reports, small series, or broad registry analyses that lack detailed tumour-level information. Key questions—such as the age-specific incidence, the distribution of locations and histologies, the prevalence of actionable molecular alterations, and the patterns of treatment, complications, recurrence, and survival—are largely unanswered, yet are critical for counselling families and planning therapy in a population with high rates of congenital heart disease, immune dysfunction, and treatment-related toxicity 7 . We therefore conducted an individual patient data meta-analysis of published and unpublished cases of brain tumours in people with DS to systematically characterise incidence, clinico-radiologic and molecular patterns, management strategies, and outcomes. Method Study Objectives The primary aim of this study is to determine the incidence, histological subtypes, and clinical outcomes of brain tumors among individuals diagnosed with Down syndrome. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Fig. 1 ). The secondary objectives of this study included evaluating survival outcomes of the patients, treatment modalities, and potential associations between specific tumor types and demographic or genetic factors within the Down syndrome population. Search Strategy The search strategy was conducted across three databases, including PubMed, Scopus, and Web of Science, to identify studies published up to 2025. The search strategy combined relevant keywords and Medical Subject Headings (MeSH) terms related to “Down syndrome,” “brain tumors,” “central nervous system neoplasms,” “glioma,” “medulloblastoma,” and other brain tumor types. The research question was developed based on the PIO (Population, Intervention, Outcome) framework. Boolean operators (AND, OR, NOT), truncations, and wildcards were used in various combinations to optimize the search process. A summary of detailed search strategy is presented in supplementary Tables . Eligibility Criteria Studies were considered eligible if they were published between 1992 and 2025 and provided original clinical data on brain tumors in individuals with Down syndrome. Eligible study designs included case reports, case series, randomized controlled trials, and relevant cohort studies. Only articles published in English, with full text access were included. Our target population comprised pediatric or adult patients with a confirmed diagnosis of Down syndrome, established through either karyotype testing or clinical evaluation. To be included, studies were required to report at least one relevant outcome, such as tumor incidence, histological subtype, treatment modality (surgery, radiotherapy, or chemotherapy), or clinical outcomes. Any studies without any sufficient data related to brain tumors in individuals with Down syndrome, non-English language publications, inaccessible full texts, and publication types limited to abstracts, editorials, commentaries, epidemiological reports, or video materials were excluded. Study Selection The databases search identified a total of 1,440 articles. Titles and abstracts were screened according to the PIO framework to determine relevance using Rayyan Software. Full-text articles were then reviewed to confirm eligibility based on the predefined inclusion and exclusion criteria. Three reviewers (Y.F.A, D.K, M.Q.A) independently assessed the quality and suitability of the included studies using standardized evaluation tools. Any disagreements between reviewers were resolved through discussion until consensus was reached. Quality Assessment For case reports and case series, the Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to assess study quality ( 8 ). This tool evaluates the clarity of clinical data, consistency in reporting, and the validity of diagnostic methods employed in each study. Data Extraction Data extraction was performed using a structured Excel spreadsheet to ensure consistency and completeness across all included studies. Three independent reviewers (Y.F.A, D.K, M.Q.A) systematically collected data on patient demographics, including age, sex, and the method used to confirm the diagnosis of Down syndrome. Other clinical information related to tumor characteristics was also extracted, including tumor type, anatomical location, histopathological diagnosis, WHO tumor grade, and molecular findings when available. Additional details regarding clinical presentation, diagnostic imaging, and therapeutic interventions—such as surgical resection, chemotherapy, and radiotherapy—were recorded. Outcome variables included overall survival, progression-free survival, treatment response, postoperative complications, and recurrence rates. To maintain data accuracy, any discrepancies between reviewers were resolved through discussion until consensus was achieved. This rigorous approach ensured that all extracted data were reliable and suitable for subsequent analysis. A detailed summary of the extracted variables and study characteristics is provided in Supplementary Tables . Statistical Analysis : Statistical analyses were conducted in R (version 4.3.0) using RStudio (2024.04.0 + 735, “Chocolate Cosmos”). For the anatomical-location–by–histology heatmap, we first constructed contingency tables of tumour location versus histological group using dplyr, tidyr, and janitor, then calculated row-wise cell counts and percentages. Association between each location–histology combination and the remaining tumours was explored with Fisher’s exact or χ² tests implemented in stats; cells with p < 0.05 and p < 0.01 were flagged with “*” and “**”, respectively, and these significance markers were overlaid on a row-normalised heatmap drawn with ggplot2 and scaled using scales. Axis labels were wrapped and ordered with forcats to optimise readability for publication. For the individual patient data (IPD) meta-analysis, we modelled time-to-death using Cox proportional hazards models in the survival package and visualised Kaplan–Meier curves with survminer. Unfavourable outcome (yes/no) was analysed using log-binomial or Poisson regression with robust standard errors (via sandwich and broom) to obtain risk ratios, applying a Haldane–Anscombe correction where needed for zero cells; study-level random-effects models and best linear unbiased predictions (BLUPs) of covariate effects were fitted with metafor and/or lme4, and displayed as forest plots using ggplot2. Results Study selection The PRISMA diagram (Fig. 1 ) outlines the systematic review workflow used to identify and select relevant studies. A total of 1,440 records were collected from various databases—Scopus (n = 732), PubMed (n = 545), and Web of Science (n = 163)—as well as from registers. After eliminating 470 duplicate entries prior to screening, 970 records were reviewed, leading to the exclusion of 910 that did not meet the criteria. Sixty reports were assessed for eligibility; three were not retrievable and thus excluded. Of these, 18 were excluded for specific reasons, including non-English language (n = 6), epidemiological focus (n = 5), abstract-only publications (n = 3), and studies unrelated to Down syndrome (n = 4). Ultimately, 39 studies satisfied all inclusion requirements and were incorporated into the final analysis ( 2 , 3 , 9 – 45 ) (Fig. 1 ). Risk of bias assessment Based on the JBI Critical Appraisal Checklist for Case Series ( supplementary files ), the overall risk of bias among the included studies was predominantly low, with most studies demonstrating a high-quality assessment score (7–8 out of 8). Only a few studies showed moderate to low quality due to incomplete reporting of clinical information or participant details. Overall, the evidence base was considered robust, reflecting consistent methodological rigor across the majority of studies. Demographic and clinical characteristics As shown in Table 1 , the cohort consisted of 41 patients with a mean age of 13.6 ± 10.5 years and a median of 12 years, spanning infancy to adulthood, with pediatric patients (< 18 years) comprising 70.7% and adults 29.3%. There was a marked male predominance (85.4%) across both age groups. Comorbidities were common, most notably neurodevelopmental disorders (36.6%), followed by perinatal/prenatal complications, structural anomalies, cardiac and endocrine issues, immune dysregulation, and prior malignancy or therapy. Presenting symptoms were predominantly neurological, led by motor deficits (48.8%), signs of raised intracranial pressure (39.0%), cerebellar symptoms (17.1%), cranial nerve or visual disturbances (12.2%), and seizures (9.8%), with symptom duration ranging widely from acute onset to nearly one year. Table 1 Demographic, clinical, and tumor characteristics of the study cohort (N = 41) Characteristic Category n (%) or summary Age at diagnosis, years Mean ± SD 13.6 ± 10.5 Median (IQR) 12 ( 11 ) Age group (years) < 1 3 (7.3%) 1–4 7 (17.1%) 5–9 6 (14.6%) 10–14 10 (24.4%) 15–17 3 (7.3%) 18–39 11 (26.8%) ≥ 40 1 (2.4%) Age category Pediatric (< 18 y) 29 (70.7%) Adult (≥ 18 y) 12 (29.3%) Sex (overall) Male 35 (85.4%) Female 6 (14.6%) Pediatric by sex Male 25 (86.2%) of pediatric group Female 4 (13.8%) of pediatric group Adult by sex Male 10 (83.3%) of adult group Female 2 (16.7%) of adult group Comorbidities (overall) * Neurodevelopmental 15 (36.6%) Perinatal/prenatal 5 (12.2%) Other structural 4 (9.8%) Cardiac 3 (7.3%) Endocrine 3 (7.3%) Prior malignancy/therapy 3 (7.3%) Immune 2 (4.9%) Presenting symptoms (overall) * Motor 20 (48.8%) Raised intracranial pressure 16 (39.0%) Cerebellar signs 7 (17.1%) Cranial nerve/visual 5 (12.2%) Seizures 4 (9.8%) Endocrine/behavioral 3 (7.3%) Symptom duration, weeks Mean ± SD 3.21 ± 10.3 Range 0–52 Tumor location (collapsed) Basal ganglia/thalamus 10 (24.4%) Posterior fossa 8 (19.5%) Cerebral hemispheric/lobar 8 (19.5%) Pineal region 4 (9.8%) Intraventricular 3 (7.3%) Cerebellopontine angle 3 (7.3%) Brainstem 1 (2.4%) Suprasellar/pituitary–infundibular 1 (2.4%) Diffuse/midline callosal 1 (2.4%) Diffuse/multifocal 1 (2.4%) Other/unspecified 1 (2.4%) Laterality Right 15 (36.6%) Left 7 (17.1%) Midline 7 (17.1%) Bilateral 3 (7.3%) Unknown 9 (22.0%) Histology group Germ cell tumor 19 (46.3%) Glial tumor 4 (9.8%) Glioma 4 (9.8%) Embryonal tumor 3 (7.3%) Ependymal tumor 2 (4.9%) Medulloblastoma 2 (4.9%) Meningioma 2 (4.9%) Choroid plexus tumor 1 (2.4%) Cyst/malformation 1 (2.4%) Cystic lesion 1 (2.4%) Lymphoma 1 (2.4%) Other/unspecified 1 (2.4%) Molecular and immunohistochemical markers (overall prevalence) * p53 IHC positive 8 (19.5%) Ki-67 high 7 (17.1%) Tumor markers panel normal 5 (12.2%) OCT4 positive 4 (9.8%) OLIG2 positive 4 (9.8%) GFAP positive 3 (7.3%) c-KIT (CD117) positive 3 (7.3%) MYC subclass 3 (7.3%) BCL6 positive 2 (4.9%) CD20 positive 2 (4.9%) KRAS mutation 2 (4.9%) Karyotype mosaicism 2 (4.9%) WNT subgroup 2 (4.9%) CD30 positive 1 (2.4%) MUM1 positive 1 (2.4%) PLAP positive 1 (2.4%) SALL4 positive 1 (2.4%) NF2 LOH 1 (2.4%) PMS2 mutation 1 (2.4%) PTCH1 mutation 1 (2.4%) RELA fusion 1 (2.4%) SHH subgroup 1 (2.4%) SMARCB1 mutation 1 (2.4%) BRAF V600E mutation 0 (0%) EGFR positive (IHC) 0 (0%) Treatment – surgery Surgery performed 29 (70.7%) Extent of resection No resection 2 (4.9%) Biopsy 4 (9.8%) STR/partial resection 11 (26.8%) GTR (gross total resection) 7 (17.1%) Unspecified 17 (41.5%) Treatment – radiotherapy Radiotherapy given 23 (56.1%) Oncologic outcomes Died 15 (36.6%) Recurrence 8 (19.5%) Outcome category Favorable: 7 (17.1%) Neutral: 8 (19.5%) Unfavorable: 8 (19.5%) Unknown: 18 (43.9%) *Percentages for comorbidities, presenting symptoms, molecular/IHC markers, treatment, and outcome variables are calculated out of the total cohort, unless otherwise specified. Tumor Characteristics Tumors demonstrated clear anatomic clustering patterns. Germ cell tumors (46.3%) occurred predominantly in the basal ganglia/thalamus and pineal region, while glial tumors and gliomas were mainly located in the cerebral hemispheres/lobar regions and brainstem. Embryonal tumors including medulloblastoma clustered in the posterior fossa. Rarer tumor types (e.g., choroid plexus, ependymal) were almost exclusively intraventricular, whereas lymphoma and unspecified histologies showed diffuse distribution. Laterality was available for most lesions, with right-sided tumors being most common (36.6%), followed by left-sided (17.1%), midline (17.1%), and bilateral (7.3%). Treatment and Management Management approaches varied widely (Table 1 ), with 70.7% undergoing surgery and procedures ranging from biopsy (9.8%) and subtotal/partial resection (26.8%) to gross total resection (17.1%), though extent was unspecified in a substantial proportion (41.5%). Radiotherapy was administered to 56.1% of patients. In multivariable analyses, including results presented in Table 2 , younger age, greater extent of resection, radiotherapy, and several histological groups showed hazard ratios below 1.0, suggesting potential protective associations; however, most confidence intervals spanned the null, underscoring limited statistical certainty regarding strong independent treatment-related effects. Table 2 Summary of Meta-analysis of Individual Patient Data Level for Survival. HR 95% CI p value Male 1.38 × 10⁸ 0 – ∞ 0.998 Neurodevelopmental comorbidity 2.15 0.40–11.60 0.374 Endocrine comorbidity 9.53 0.27–339.00 0.216 Cardiac comorbidity 1.35 0.17–10.30 0.776 Immune disorder 16.52 0.35–771.00 0.153 Prior malignancy / anti-cancer therapy 7.83 0.75–81.50 0.085 Significant perinatal / prenatal history 3.36 0.54–21.00 0.194 Other structural anomalies 0.55 0.06–5.36 0.608 Motor symptoms at presentation 0.49 0.11–2.24 0.359 Cerebellar symptoms at presentation 0.09 0.00–1.63 0.102 Seizures at presentation 0.58 0.06–5.19 0.626 Raised intracranial pressure symptoms 1.85 0.49–7.04 0.364 Cranial nerve / visual symptoms 0.27 0.02–3.72 0.327 Endocrine / behavioural symptoms 4.96 0.34–73.50 0.244 Primary tumour location Brainstem 3.04 0.38–24.22 0.293 Cerebellopontine angle 0.00 0 – ∞ 0.997 Cerebral hemispheric / lobar 2.19 0.70–6.87 0.181 Diffuse / midline callosal 0.50 0 – ∞ 1.000 Diffuse / multifocal 1.00 0 – ∞ 1.000 Intraventricular 6.44 0.75–55.45 0.090 Intraventricular (4th ventricle)* 1.50 × 10⁸ 1.85×10⁷ – 1.22×10⁹ < 0.001 Other / unspecified 0.00 0 – ∞ 0.999 Pineal region* 2.84 × 10⁸ 5.83×10⁷ – 1.38×10⁹ < 0.001 Posterior fossa (not otherwise specified) 1.00 0 – ∞ 1.000 Posterior fossa – cerebellar hemisphere 0.00 0 – ∞ 0.998 Posterior fossa – cerebellar hemispheric 0.00 0 – ∞ 1.000 Posterior fossa – unspecified 0.00 0 – ∞ 0.997 Posterior fossa – vermis / 4th ventricle* 44.13 4.75–409.98 < 0.001 Suprasellar / pituitary–infundibular 1.00 0 – ∞ 1.000 Tumour laterality Left* 3.13 × 10⁷ 6.64×10⁶ – 1.47×10⁸ < 0.001 Midline 1.00 0.26–3.80 1.000 Right* 5.94 × 10⁷ 2.10×10⁷ – 1.68×10⁸ < 0.001 Unknown* 3.53 × 10⁷ 9.62×10⁶ – 1.30×10⁸ < 0.001 Histological tumor group Cyst / malformation 0.00 0 – ∞ 0.998 Cystic lesion 2.39 0.26–22.25 0.444 Embryonal tumour 0.00 0 – ∞ 0.997 Ependymal tumour 0.31 0.04–2.43 0.263 Germ cell tumour* 0.09 0.03–0.28 < 0.001 Glial tumour 0.22 0.06–0.80 0.022 Glioma 0.24 0.05–1.07 0.061 Lymphoma 0.00 0 – ∞ 1.000 Medulloblastoma 0.27 0.03–2.10 0.209 Meningioma 0.00 0 – ∞ 0.997 Other / unspecified 0.00 0 – ∞ 0.998 Genetic / molecular alterations NF2 loss of heterozygosity (NF2 LOH) 0.00 0 – ∞ 0.998 SMARCB1 mutation 0.00 0 – ∞ 0.998 RELA fusion 0.00 0 – ∞ 0.998 WNT subgroup 1.18 0.15–9.13 0.873 SHH subgroup 0.00 0 – ∞ 0.998 PTCH1 mutation 0.00 0 – ∞ 0.998 KRAS mutation 0.00 0 – ∞ 0.998 PMS2 mutation 0.00 0 – ∞ 0.998 BRAF V600E mutation NA NA NA MYC subclass 0.96 0.12–7.42 0.971 Germ cell tumour markers (IHC) PLAP positive 0.00 0 – ∞ 0.998 cKIT positive 0.96 0.12–7.42 0.971 OCT4 positive 0.63 0.08–4.87 0.658 SALL4 positive 16.92 1.82–157.60 0.013 Lymphoma markers (IHC) CD30 positive 0.00 0 – ∞ 0.998 CD20 positive 0.00 0 – ∞ 0.998 BCL6 positive 0.00 0 – ∞ 0.998 MUM1 positive 0.00 0 – ∞ 0.998 Glial / other tumour markers GFAP positive 5.33 1.09–26.17 0.039 EGFR positive NA NA NA OLIG2 positive 0.51 0.07–3.95 0.519 High Ki-67 index 0.91 0.20–4.08 0.905 Serum/CSF tumour markers normal 1.40 0.31–6.26 0.661 p53 mutation absent (reported) 1.68 0.52–5.37 0.384 p53 IHC positive 2.01 0.62–6.52 0.247 Surgery Surgery performed (yes) 0.89 0.29–2.66 0.828 Extent of resection Gross total resection (GTR) 1.09 × 10⁸ 0 – ∞ 0.998 No resection 2.10 × 10⁸ 0 – ∞ 0.998 Subtotal / partial resection (STR/partial) 1.00 × 10⁸ 0 – ∞ 0.998 Extent of resection unspecified 6.50 × 10⁷ 0 – ∞ 0.998 Radiotherapy Radiotherapy given (yes) 0.67 0.24–1.86 0.442 Disease course Recurrence 2.98 1.03–8.63 0.044 Outcome category: neutral 4.10 0.46–36.82 0.207 Outcome category: unfavorable 5.71 0.63–52.09 0.122 Outcome category: unknown 2.68 0.32–22.37 0.363 Surgery Surgery performed 0.89 0.29–2.66 0.828 Extent of resection Gross total resection (GTR) 1.09 × 10⁸ 0 – ∞ 0.998 No resection 2.10 × 10⁸ 0 – ∞ 0.998 Subtotal / partial resection (STR/partial) 1.00 × 10⁸ 0 – ∞ 0.998 Extent of resection unspecified 6.50 × 10⁷ 0 – ∞ 0.998 Radiotherapy Radiotherapy given (yes) 0.67 0.24–1.86 0.442 Recurrence 2.98 1.03–8.63 0.044 Disease course Neutral 4.10 0.46–36.82 0.207 Unfavourable 5.71 0.63–52.09 0.122 Unknown 2.68 0.32–22.37 0.363 * Statistically significant (p < 0.05). Outcomes Across the cohort, 36.6% of patients died and 19.5% experienced recurrence, with outcomes categorized as favorable, neutral, unfavorable, or unknown. In Table 2 and Fig. 2 , several covariates reached statistical significance, including markedly elevated hazard ratios for intraventricular 4th-ventricular tumours (HR 1.50 × 10⁸), pineal region tumours (2.84 × 10⁸), posterior fossa lesions (44.13), and lateralized lesions compared with midline, as well as protective effects for germ cell and glial tumours. Recurrence, GFAP positivity, and SALL4 expression were also significantly associated with poorer outcomes. BLUP-derived risk ratio estimates (Fig. 5 ) ranged widely and often crossed the null, indicating considerable uncertainty. The Kaplan–Meier curve (Fig. 5 ) showed an early sharp drop in survival during the first year, followed by a relative plateau, with 5-year overall survival remaining slightly above 50%; the median survival was not reached, and confidence intervals widened substantially beyond 24 months due to decreasing numbers at risk. Molecular and Immunohistochemical Findings Molecular analysis, when available, consistently confirmed trisomy 21 across informative cases, with additional alterations spanning KRAS, PMS2, PTCH1, NF2, SMARCB1, RELA fusion, and SHH or WNT subgroup assignments, though no recurrent secondary molecular driver emerged (Table 1 ). Immunohistochemical profiles aligned with expected tumour lineages—PLAP/OCT4/SALL4/c-KIT in germ cell tumours; CD20/BCL6/MUM1 in lymphoma; GFAP/OLIG2 in glial tumours—while proliferative markers such as Ki-67 and p53 positivity were variably expressed. These findings reflect a heterogeneous but biologically coherent molecular landscape consistent with the tumour types represented, further illustrated in Fig. 2 . Discussion In our pooled IPD, we found that brain tumors in people with Down syndrome cluster in deep and midline structures, especially the basal ganglia/thalamus, pineal region, and posterior fossa vermis/4th ventricle, and that these locations are over-represented among germ cell tumors, embryonal tumors and gliomas. This pattern broadly supports prior reports that intracranial germ cell tumors preferentially arise in the pineal and suprasellar regions and that medulloblastoma and related embryonal tumors are typically posterior fossa/4th-ventricular lesions 46,47 , while also aligning with case reports of basal ganglia germinomas and deep-seated gliomas in Down syndrome. These sites are intimately related to CSF pathways, deep venous drainage, and the brainstem, so even modest tumor volumes can rapidly produce obstructive hydrocephalus, raised intracranial pressure and cranial neuropathies 48–50 ; this provides a plausible mechanistic explanation for the prominent motor, cerebellar and cranial nerve presentations, as well as for the substantial early mortality seen in our Kaplan–Meier curve. With respect to survival, we found that tumor site and histology are the main statistically significant determinants of outcome, whereas most clinical comorbidities and presenting symptoms did not reach significance. Specifically, intraventricular 4th-ventricular tumors (HR 1.50×10⁸, 95% CI 1.85×10⁷–1.22×10⁹, p < 0.001), pineal tumors (HR 2.84×10⁸, 95% CI 5.83×10⁷–1.38×10⁹, p < 0.001), and posterior fossa vermis/4th-ventricle lesions (HR 44.13, 95% CI 4.75–409.98, p < 0.001) were associated with a markedly increased hazard of death, while germ cell tumors overall were associated with a substantially reduced hazard (HR 0.09, 95% CI 0.03–0.28, p < 0.001) and glial tumors also showed a protective effect (HR 0.22, 95% CI 0.06–0.80, p = 0.022). These findings are broadly concordant with the general pediatric neuro-oncology literature, where germinomas and many non–glioblastoma glial tumors are highly chemo radiosensitive with favorable long-term survival 51 , whereas 4th-ventricular embryonal tumors and high-grade gliomas carry a poor prognosis. This contrast reflects both tumor biology (e.g. intrinsic treatment sensitivity vs. infiltrative behaviour) and anatomy: pineal/4th-ventricular masses are harder to resect completely without brainstem or cerebellar injury 52 , and small residual disease in these compartments can have disproportionate clinical consequences. At the molecular and immunophenotypic level, our data suggest that only a few markers currently add statistically robust prognostic information, while most genetic alterations did not reach significance in this small cohort. SALL4 positivity, a marker of malignant germ cell components, was associated with a significantly increased hazard of death (HR 16.92, 95% CI 1.82–157.60, p = 0.013), and GFAP positivity was likewise linked to poorer survival (HR 5.33, 95% CI 1.09–26.17, p = 0.039), whereas other tested alterations (e.g. WNT/SHH subgrouping, KRAS/PMS2, NF2, SMARCB1) did not show clear prognostic effects. This partially supports existing evidence that, in Down syndrome, trisomy 21 is a constant background event while additional oncogenic drivers are heterogeneous rather than converging on a single dominant “ second hit .” These patterns are consistent with the idea that brain tumors in Down syndrome arise from the same germ cell, glial, or embryonal lineages as in euploid patients 53,54 , but on a chromosomal-21–enriched background that may subtly modulate tumor microenvironment, immune surveillance, and DNA damage responses without fully redefining lineage-specific behavior. Clinical Applicability Even though all included studies were case reports or small case series, in such a rare population this pooled individual patient data meta-analysis currently represents the most robust evidence base available to guide clinical decision-making. The synthesis shows that tumor type and anatomical site strongly shape presentation and survival, whereas traditional comorbidities (cardiac, endocrine, immune) are less clearly prognostic. This means that new focal neurological deficits, symptoms of raised intracranial pressure, or neuroendocrine changes in individuals with Down syndrome should trigger prompt, targeted neuroimaging of high-risk regions, and that deep midline germ cell tumours or glial tumours may warrant aggressive but carefully tailored multimodal therapy, while intraventricular and posterior fossa vermian lesions should be managed as particularly high-risk entities. Study Limitaiton This work is constrained by the fact that all included primary reports are case reports or case series, which are intrinsically prone to selection and publication bias toward atypical or severe presentations and limit control for confounding. The small sample size within many strata, together with sparse events, led to unstable hazard ratio estimates in the IPD meta-analysis, with several parameters yielding extreme values and confidence intervals extending from 0 to infinity, reflecting quasi-complete separation rather than true biological effects 55 . Heterogeneity in diagnostic era, imaging, histopathological classification, molecular testing, and treatment protocols, as well as incomplete and variably reported follow-up, further restricts the precision and generalizability of these findings. Conclusion The following IPD meta-analysis highlights a distinctive but heterogeneous landscape of brain tumours in people with Down syndrome, characterised by a predominance of deep and midline lesions, an over-representation of germ cell tumours, medulloblastoma and high-grade gliomas, and survival that is strongly influenced by anatomical location, histology and recurrence rather than by baseline comorbidities alone. While some entities appear to retain relatively favourable outcomes, intraventricular, pineal and posterior fossa vermian lesions carry a markedly increased hazard of death despite intensive therapy. These findings support a tailored, anatomy- and histology-guided approach to diagnosis and treatment in Down syndrome, and they underscore the need for prospective, registry-based collaborative studies to refine risk stratification, optimise neurosurgical and oncological strategies, and better define long-term functional outcomes in this vulnerable group. Declarations All of the authors declare that they have all participated in the design, execution, and analysis of the paper, and that they have approved the final version. Additionally, the material described is not under publication or consideration for publication elsewhere. Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Consent: Our article does not require patient consent. Availability of data and materials: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing Interest: The authors have no conflicts of interest to declare. Funding: No funds were granted for this paper. Author’s Contribution: Y.F.A conceptualized the study, finalized the topic, perform screening, major contribution to manuscript writing, drafting, literature search, discussion writing and provided overall supervision. J.H.W cleaned the data, carried out analysis, compiled the results, and compiled the manuscript. D.K carried out data extraction and quality assessment. M.Q.A carried out data extraction and quality assessment. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8168623","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":606282978,"identity":"2a8173dd-6b85-432f-b5de-54f0528fc51c","order_by":0,"name":"Yasser F Almealawy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABD0lEQVRIiWNgGAWjYDACdhBRgODLgYgDD/BpYQYRBgi+MVhLAilaEhtAJD4t/M3ciQ9+GNglbriR/Pjjj4p76fPDDj8E2mInp9uAXYvEYd7Nhj0GyUAtaWbSPGeKczfeTjMAakk2NjuAw5rDvNskeAyYczfcSDBjZmxLyN04OwGk5UDiNhxa5A/zbv/5x6AeqCX988ef/xLSDWenf8CrxQBoCzOPwWGglhwDCd6GhAR56Rz8thgC/SItY3C8fuaZN2XSPMcSDDdI5xQcSDDA7Re5470bP76pqDbmO56++eOPmgR5+dnpmz98qLCTw+l9GFC4kAB1KlilAW6VcCDfDzVUvoEI1aNgFIyCUTCiAAAl5mforZUM9AAAAABJRU5ErkJggg==","orcid":"","institution":"university of Kufa","correspondingAuthor":true,"prefix":"","firstName":"Yasser","middleName":"F","lastName":"Almealawy","suffix":""},{"id":606282979,"identity":"4b594c96-39ef-402e-aa83-bff3b3b843fa","order_by":1,"name":"Jeremiah Hilkiah Wijaya","email":"","orcid":"","institution":"Siloam Hospital Lippo Village","correspondingAuthor":false,"prefix":"","firstName":"Jeremiah","middleName":"Hilkiah","lastName":"Wijaya","suffix":""},{"id":606282980,"identity":"1ee3e770-c38e-4deb-823d-9c3a4ca8d7e5","order_by":2,"name":"Danisha Kumar","email":"","orcid":"","institution":"Dow University of Health Sciences","correspondingAuthor":false,"prefix":"","firstName":"Danisha","middleName":"","lastName":"Kumar","suffix":""},{"id":606282981,"identity":"6c0aa710-3a04-4496-852a-89ee065fdeda","order_by":3,"name":"Mohammed Q. Alibraheemi","email":"","orcid":"","institution":"Carol Davila University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"Q.","lastName":"Alibraheemi","suffix":""},{"id":606282982,"identity":"7e787055-41ad-495d-b9fb-1b6fee0f4e3a","order_by":4,"name":"Ranya Nawfal Smesim","email":"","orcid":"","institution":"university of Kufa","correspondingAuthor":false,"prefix":"","firstName":"Ranya","middleName":"Nawfal","lastName":"Smesim","suffix":""},{"id":606282983,"identity":"818392a5-3281-4c51-adb0-e25fe1e3b303","order_by":5,"name":"Khadeja Alrefaie","email":"","orcid":"","institution":"Royal College of Surgeons in Ireland","correspondingAuthor":false,"prefix":"","firstName":"Khadeja","middleName":"","lastName":"Alrefaie","suffix":""},{"id":606282984,"identity":"4969fe56-f099-47bf-846f-add594a55537","order_by":6,"name":"Saad Hulou","email":"","orcid":"","institution":"University of Kentucky","correspondingAuthor":false,"prefix":"","firstName":"Saad","middleName":"","lastName":"Hulou","suffix":""}],"badges":[],"createdAt":"2025-11-21 02:08:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8168623/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8168623/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104888050,"identity":"87148af8-3365-4ec6-8b6f-d602c50522e9","added_by":"auto","created_at":"2026-03-18 10:13:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":252777,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u0026nbsp;\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8168623/v1/88c08f2fa5c13e860182e918.png"},{"id":104888024,"identity":"b0a608c9-c9b6-4185-bc77-e776d5b92cfd","added_by":"auto","created_at":"2026-03-18 10:13:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":391278,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u0026nbsp;\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8168623/v1/5ee18fa1fdd357c22c24d44e.png"},{"id":104888022,"identity":"19ce0f55-45f0-4f94-b3a2-d510c76c70cb","added_by":"auto","created_at":"2026-03-18 10:13:08","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1418695,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u0026nbsp;\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8168623/v1/ba22d3eb12035afb36eb8eda.png"},{"id":104888015,"identity":"12b2b050-e3b4-4c24-a145-129b33069cf0","added_by":"auto","created_at":"2026-03-18 10:13:05","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":344192,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u0026nbsp;\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8168623/v1/2aac9db6b5a326498a998593.png"},{"id":104888020,"identity":"1e19d6d5-d64f-4692-8c94-8dddc3e73336","added_by":"auto","created_at":"2026-03-18 10:13:06","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":165371,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u0026nbsp;\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8168623/v1/c150b73a551e0f913b5beac0.png"},{"id":105034337,"identity":"18c231a1-7218-47b1-98d2-800eb76b0511","added_by":"auto","created_at":"2026-03-20 07:23:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3667780,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8168623/v1/787b8d36-dc16-4a4a-bb87-022ebbda2248.pdf"},{"id":104887959,"identity":"6f6f8cab-e1d2-4663-8f5a-5db262f41229","added_by":"auto","created_at":"2026-03-18 10:13:04","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":56965,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8168623/v1/8290fe37da0f2745bf1fdea2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Brain Tumours in Individuals with Down Syndrome: An Individual Patient Data Meta-analysis of Incidence, Patterns and Outcomes","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBrain tumours in individuals with Down syndrome (DS) sit at the intersection of a common genetic condition and a highly unusual cancer risk profile. DS affects roughly 1 in 700 live births and is the most frequent chromosomal abnormality worldwide\u003csup\u003e1\u003c/sup\u003e. As survival has improved into middle and older adulthood, cancer has become a key contributor to morbidity and mortality in this population. Epidemiologic studies consistently show a 10\u0026ndash;20-fold increased risk of acute leukaemias, contrasted with an approximately twofold lower risk of solid tumours compared with the general population, and a 50\u0026ndash;100-fold lower likelihood of dying from a solid tissue cancer\u003csup\u003e2\u003c/sup\u003e. Within this solid-tumour deficit, brain tumours appear particularly rare, with only small registry series and scattered case reports suggesting that central nervous system (CNS) neoplasms represent a very small fraction of cancers in DS and that their true incidence, spectrum, and outcomes remain poorly defined\u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe distinctive tumour pattern in DS is thought to reflect the dosage effect of triplicated chromosome 21 genes, which alters developmental biology, immune function, and oncogenic signalling. Several chromosome 21\u0026ndash;encoded proteins, including DYRK1A\u003csup\u003e4\u003c/sup\u003e and RCAN1 (DSCR1), inhibit the calcineurin\u0026ndash;NFAT pathway and angiogenesis, and are proposed to confer systemic protection against many solid tumours. Additional mechanisms such as overexpression of candidate tumour suppressors (e.g. ETS2)\u003csup\u003e5\u003c/sup\u003e, disturbed metabolism, increased apoptosis, and impaired neo-angiogenesis may further lower solid-tumour risk in DS. However, CNS tumour biology in DS is unlikely to be uniformly protective. Multi-institutional data indicate that primary CNS germ cell tumours (GCTs) are the most common CNS neoplasms in DS, and that DS and other chromosomal sex aneuploidies are over-represented among patients with intracranial GCTs\u003csup\u003e6\u003c/sup\u003e; medulloblastoma and other embryonal or glial tumours, while rare, are increasingly reported. These observations suggest that trisomy 21 may differentially modulate specific neurodevelopmental lineages and signalling pathways (e.g. SHH, WNT, MYC) rather than conferring uniform protection across all brain tumour types.\u003c/p\u003e \u003cp\u003eDespite these clinical and biological implications, data on brain tumours in DS remain fragmented, limited to isolated case reports, small series, or broad registry analyses that lack detailed tumour-level information. Key questions\u0026mdash;such as the age-specific incidence, the distribution of locations and histologies, the prevalence of actionable molecular alterations, and the patterns of treatment, complications, recurrence, and survival\u0026mdash;are largely unanswered, yet are critical for counselling families and planning therapy in a population with high rates of congenital heart disease, immune dysfunction, and treatment-related toxicity\u003csup\u003e7\u003c/sup\u003e. We therefore conducted an individual patient data meta-analysis of published and unpublished cases of brain tumours in people with DS to systematically characterise incidence, clinico-radiologic and molecular patterns, management strategies, and outcomes.\u003c/p\u003e"},{"header":"Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Objectives\u003c/h2\u003e \u003cp\u003eThe primary aim of this study is to determine the incidence, histological subtypes, and clinical outcomes of brain tumors among individuals diagnosed with Down syndrome. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The secondary objectives of this study included evaluating survival outcomes of the patients, treatment modalities, and potential associations between specific tumor types and demographic or genetic factors within the Down syndrome population.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSearch Strategy\u003c/h3\u003e\n\u003cp\u003eThe search strategy was conducted across three databases, including PubMed, Scopus, and Web of Science, to identify studies published up to 2025. The search strategy combined relevant keywords and Medical Subject Headings (MeSH) terms related to \u0026ldquo;Down syndrome,\u0026rdquo; \u0026ldquo;brain tumors,\u0026rdquo; \u0026ldquo;central nervous system neoplasms,\u0026rdquo; \u0026ldquo;glioma,\u0026rdquo; \u0026ldquo;medulloblastoma,\u0026rdquo; and other brain tumor types. The research question was developed based on the PIO (Population, Intervention, Outcome) framework. Boolean operators (AND, OR, NOT), truncations, and wildcards were used in various combinations to optimize the search process. A summary of detailed search strategy is presented in supplementary \u003cb\u003eTables\u003c/b\u003e.\u003c/p\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003e Studies were considered eligible if they were published between 1992 and 2025 and provided original clinical data on brain tumors in individuals with Down syndrome. Eligible study designs included case reports, case series, randomized controlled trials, and relevant cohort studies. Only articles published in English, with full text access were included.\u003c/p\u003e \u003cp\u003eOur target population comprised pediatric or adult patients with a confirmed diagnosis of Down syndrome, established through either karyotype testing or clinical evaluation. To be included, studies were required to report at least one relevant outcome, such as tumor incidence, histological subtype, treatment modality (surgery, radiotherapy, or chemotherapy), or clinical outcomes.\u003c/p\u003e \u003cp\u003eAny studies without any sufficient data related to brain tumors in individuals with Down syndrome, non-English language publications, inaccessible full texts, and publication types limited to abstracts, editorials, commentaries, epidemiological reports, or video materials were excluded.\u003c/p\u003e\n\u003ch3\u003eStudy Selection\u003c/h3\u003e\n\u003cp\u003eThe databases search identified a total of 1,440 articles. Titles and abstracts were screened according to the PIO framework to determine relevance using Rayyan Software. Full-text articles were then reviewed to confirm eligibility based on the predefined inclusion and exclusion criteria.\u003c/p\u003e \u003cp\u003eThree reviewers (Y.F.A, D.K, M.Q.A) independently assessed the quality and suitability of the included studies using standardized evaluation tools. Any disagreements between reviewers were resolved through discussion until consensus was reached.\u003c/p\u003e\n\u003ch3\u003eQuality Assessment\u003c/h3\u003e\n\u003cp\u003eFor case reports and case series, the Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to assess study quality (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This tool evaluates the clarity of clinical data, consistency in reporting, and the validity of diagnostic methods employed in each study.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eData Extraction\u003c/h2\u003e \u003cp\u003eData extraction was performed using a structured Excel spreadsheet to ensure consistency and completeness across all included studies. Three independent reviewers (Y.F.A, D.K, M.Q.A) systematically collected data on patient demographics, including age, sex, and the method used to confirm the diagnosis of Down syndrome.\u003c/p\u003e \u003cp\u003eOther clinical information related to tumor characteristics was also extracted, including tumor type, anatomical location, histopathological diagnosis, WHO tumor grade, and molecular findings when available. Additional details regarding clinical presentation, diagnostic imaging, and therapeutic interventions\u0026mdash;such as surgical resection, chemotherapy, and radiotherapy\u0026mdash;were recorded.\u003c/p\u003e \u003cp\u003eOutcome variables included overall survival, progression-free survival, treatment response, postoperative complications, and recurrence rates. To maintain data accuracy, any discrepancies between reviewers were resolved through discussion until consensus was achieved. This rigorous approach ensured that all extracted data were reliable and suitable for subsequent analysis.\u003c/p\u003e \u003cp\u003eA detailed summary of the extracted variables and study characteristics is provided in \u003cb\u003eSupplementary Tables\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eStatistical Analysis\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eStatistical analyses were conducted in R (version 4.3.0) using RStudio (2024.04.0\u0026thinsp;+\u0026thinsp;735, \u0026ldquo;Chocolate Cosmos\u0026rdquo;). For the anatomical-location\u0026ndash;by\u0026ndash;histology heatmap, we first constructed contingency tables of tumour location versus histological group using dplyr, tidyr, and janitor, then calculated row-wise cell counts and percentages. Association between each location\u0026ndash;histology combination and the remaining tumours was explored with Fisher\u0026rsquo;s exact or χ\u0026sup2; tests implemented in stats; cells with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 and p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 were flagged with \u0026ldquo;*\u0026rdquo; and \u0026ldquo;**\u0026rdquo;, respectively, and these significance markers were overlaid on a row-normalised heatmap drawn with ggplot2 and scaled using scales. Axis labels were wrapped and ordered with forcats to optimise readability for publication.\u003c/p\u003e \u003cp\u003eFor the individual patient data (IPD) meta-analysis, we modelled time-to-death using Cox proportional hazards models in the survival package and visualised Kaplan\u0026ndash;Meier curves with survminer. Unfavourable outcome (yes/no) was analysed using log-binomial or Poisson regression with robust standard errors (via sandwich and broom) to obtain risk ratios, applying a Haldane\u0026ndash;Anscombe correction where needed for zero cells; study-level random-effects models and best linear unbiased predictions (BLUPs) of covariate effects were fitted with metafor and/or lme4, and displayed as forest plots using ggplot2.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStudy selection\u003c/h2\u003e \u003cp\u003eThe PRISMA diagram (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e) outlines the systematic review workflow used to identify and select relevant studies. A total of 1,440 records were collected from various databases\u0026mdash;Scopus (n\u0026thinsp;=\u0026thinsp;732), PubMed (n\u0026thinsp;=\u0026thinsp;545), and Web of Science (n\u0026thinsp;=\u0026thinsp;163)\u0026mdash;as well as from registers. After eliminating 470 duplicate entries prior to screening, 970 records were reviewed, leading to the exclusion of 910 that did not meet the criteria. Sixty reports were assessed for eligibility; three were not retrievable and thus excluded. Of these, 18 were excluded for specific reasons, including non-English language (n\u0026thinsp;=\u0026thinsp;6), epidemiological focus (n\u0026thinsp;=\u0026thinsp;5), abstract-only publications (n\u0026thinsp;=\u0026thinsp;3), and studies unrelated to Down syndrome (n\u0026thinsp;=\u0026thinsp;4). Ultimately, 39 studies satisfied all inclusion requirements and were incorporated into the final analysis (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41 CR42 CR43 CR44\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eRisk of bias assessment\u003c/h2\u003e \u003cp\u003eBased on the JBI Critical Appraisal Checklist for Case Series (\u003cb\u003esupplementary files\u003c/b\u003e), the overall risk of bias among the included studies was predominantly low, with most studies demonstrating a high-quality assessment score (7\u0026ndash;8 out of 8). Only a few studies showed moderate to low quality due to incomplete reporting of clinical information or participant details. Overall, the evidence base was considered robust, reflecting consistent methodological rigor across the majority of studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and clinical characteristics\u003c/h2\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the cohort consisted of 41 patients with a mean age of 13.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5 years and a median of 12 years, spanning infancy to adulthood, with pediatric patients (\u0026lt;\u0026thinsp;18 years) comprising 70.7% and adults 29.3%. There was a marked male predominance (85.4%) across both age groups. Comorbidities were common, most notably neurodevelopmental disorders (36.6%), followed by perinatal/prenatal complications, structural anomalies, cardiac and endocrine issues, immune dysregulation, and prior malignancy or therapy. Presenting symptoms were predominantly neurological, led by motor deficits (48.8%), signs of raised intracranial pressure (39.0%), cerebellar symptoms (17.1%), cranial nerve or visual disturbances (12.2%), and seizures (9.8%), with symptom duration ranging widely from acute onset to nearly one year.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic, clinical, and tumor characteristics of the study cohort (N\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en (%) or summary\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at diagnosis, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge group (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u0026ndash;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (14.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u0026ndash;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (24.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u0026ndash;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u0026ndash;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (26.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePediatric (\u0026lt;\u0026thinsp;18 y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (70.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdult (\u0026ge;\u0026thinsp;18 y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (29.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (overall)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (85.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (14.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePediatric by sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (86.2%) of pediatric group\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (13.8%) of pediatric group\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdult by sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (83.3%) of adult group\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (16.7%) of adult group\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eComorbidities (overall)\u003c/em\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeurodevelopmental\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (36.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePerinatal/prenatal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther structural\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCardiac\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEndocrine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrior malignancy/therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eImmune\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u003cem\u003ePresenting symptoms (overall)\u003c/em\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMotor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (48.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRaised intracranial pressure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (39.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCerebellar signs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCranial nerve/visual\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSeizures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEndocrine/behavioral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSymptom duration, weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.21\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"10\" rowspan=\"11\"\u003e \u003cp\u003eTumor location (collapsed)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBasal ganglia/thalamus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (24.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePosterior fossa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (19.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCerebral hemispheric/lobar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (19.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePineal region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntraventricular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCerebellopontine angle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrainstem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuprasellar/pituitary\u0026ndash;infundibular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiffuse/midline callosal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiffuse/multifocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther/unspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaterality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (36.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMidline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (22.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGerm cell tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (46.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGlial tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGlioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEmbryonal tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEpendymal tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedulloblastoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeningioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChoroid plexus tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCyst/malformation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCystic lesion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther/unspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"12\" rowspan=\"13\"\u003e \u003cp\u003e\u003cem\u003eMolecular and immunohistochemical markers (overall prevalence)\u003c/em\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep53 IHC positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (19.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKi-67 high\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTumor markers panel normal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOCT4 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOLIG2 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGFAP positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ec-KIT (CD117) positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMYC subclass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCL6 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCD20 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKRAS mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKaryotype mosaicism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWNT subgroup\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCD30 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMUM1 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePLAP positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSALL4 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNF2 LOH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePMS2 mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePTCH1 mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRELA fusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSHH subgroup\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSMARCB1 mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBRAF V600E mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEGFR positive (IHC)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment \u0026ndash; surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSurgery performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (70.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtent of resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBiopsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSTR/partial resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (26.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGTR (gross total resection)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (41.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment \u0026ndash; radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRadiotherapy given\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (56.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOncologic outcomes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (36.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRecurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (19.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOutcome category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFavorable: 7 (17.1%)\u003c/p\u003e \u003cp\u003eNeutral: 8 (19.5%)\u003c/p\u003e \u003cp\u003eUnfavorable: 8 (19.5%)\u003c/p\u003e \u003cp\u003eUnknown: 18 (43.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e*Percentages for comorbidities, presenting symptoms, molecular/IHC markers, treatment, and outcome variables are calculated out of the total cohort, unless otherwise specified.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eTumor Characteristics\u003c/h2\u003e \u003cp\u003eTumors demonstrated clear anatomic clustering patterns. Germ cell tumors (46.3%) occurred predominantly in the basal ganglia/thalamus and pineal region, while glial tumors and gliomas were mainly located in the cerebral hemispheres/lobar regions and brainstem. Embryonal tumors including medulloblastoma clustered in the posterior fossa. Rarer tumor types (e.g., choroid plexus, ependymal) were almost exclusively intraventricular, whereas lymphoma and unspecified histologies showed diffuse distribution. Laterality was available for most lesions, with right-sided tumors being most common (36.6%), followed by left-sided (17.1%), midline (17.1%), and bilateral (7.3%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eTreatment and Management\u003c/h2\u003e \u003cp\u003eManagement approaches varied widely (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), with 70.7% undergoing surgery and procedures ranging from biopsy (9.8%) and subtotal/partial resection (26.8%) to gross total resection (17.1%), though extent was unspecified in a substantial proportion (41.5%). Radiotherapy was administered to 56.1% of patients. In multivariable analyses, including results presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, younger age, greater extent of resection, radiotherapy, and several histological groups showed hazard ratios below 1.0, suggesting potential protective associations; however, most confidence intervals spanned the null, underscoring limited statistical certainty regarding strong independent treatment-related effects.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of Meta-analysis of Individual Patient Data Level for Survival.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.38 \u0026times; 10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurodevelopmental comorbidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.40\u0026ndash;11.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.374\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocrine comorbidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.27\u0026ndash;339.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.216\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac comorbidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.17\u0026ndash;10.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.776\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmune disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.35\u0026ndash;771.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.153\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior malignancy / anti-cancer therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.75\u0026ndash;81.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSignificant perinatal / prenatal history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.54\u0026ndash;21.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.194\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther structural anomalies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.06\u0026ndash;5.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.608\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMotor symptoms at presentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.11\u0026ndash;2.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.359\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebellar symptoms at presentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00\u0026ndash;1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeizures at presentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.06\u0026ndash;5.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.626\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRaised intracranial pressure symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.49\u0026ndash;7.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.364\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCranial nerve / visual symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.02\u0026ndash;3.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.327\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocrine / behavioural symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.34\u0026ndash;73.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.244\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrimary tumour location\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrainstem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.38\u0026ndash;24.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.293\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebellopontine angle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebral hemispheric / lobar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.70\u0026ndash;6.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.181\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiffuse / midline callosal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiffuse / multifocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraventricular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.75\u0026ndash;55.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.090\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraventricular (4th ventricle)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.50 \u0026times; 10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.85\u0026times;10⁷ \u0026ndash; 1.22\u0026times;10⁹\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e\u0026lt;\u0026thinsp;0.001\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther / unspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePineal region*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.84 \u0026times; 10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.83\u0026times;10⁷ \u0026ndash; 1.38\u0026times;10⁹\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e\u0026lt;\u0026thinsp;0.001\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePosterior fossa (not otherwise specified)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePosterior fossa \u0026ndash; cerebellar hemisphere\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePosterior fossa \u0026ndash; cerebellar hemispheric\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePosterior fossa \u0026ndash; unspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePosterior fossa \u0026ndash; vermis / 4th ventricle*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.75\u0026ndash;409.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuprasellar / pituitary\u0026ndash;infundibular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumour laterality\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.13 \u0026times; 10⁷\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.64\u0026times;10⁶ \u0026ndash; 1.47\u0026times;10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMidline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.26\u0026ndash;3.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.94 \u0026times; 10⁷\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.10\u0026times;10⁷ \u0026ndash; 1.68\u0026times;10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.53 \u0026times; 10⁷\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.62\u0026times;10⁶ \u0026ndash; 1.30\u0026times;10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistological tumor group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyst / malformation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCystic lesion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.26\u0026ndash;22.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.444\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmbryonal tumour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpendymal tumour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.04\u0026ndash;2.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.263\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGerm cell tumour*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03\u0026ndash;0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlial tumour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.06\u0026ndash;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.05\u0026ndash;1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.061\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedulloblastoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03\u0026ndash;2.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.209\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeningioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther / unspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGenetic / molecular alterations\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNF2 loss of heterozygosity (NF2 LOH)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSMARCB1 mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRELA fusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWNT subgroup\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.15\u0026ndash;9.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.873\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSHH subgroup\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTCH1 mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKRAS mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePMS2 mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBRAF V600E mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMYC subclass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.12\u0026ndash;7.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.971\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGerm cell tumour markers (IHC)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLAP positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecKIT positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.12\u0026ndash;7.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.971\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOCT4 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.08\u0026ndash;4.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.658\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSALL4 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.82\u0026ndash;157.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymphoma markers (IHC)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD30 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD20 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCL6 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMUM1 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlial / other tumour markers\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGFAP positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.09\u0026ndash;26.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEGFR positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOLIG2 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;3.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.519\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh Ki-67 index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.20\u0026ndash;4.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.905\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum/CSF tumour markers normal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.31\u0026ndash;6.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.661\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep53 mutation absent (reported)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.52\u0026ndash;5.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep53 IHC positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.62\u0026ndash;6.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.247\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery performed (yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.29\u0026ndash;2.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.828\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExtent of resection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGross total resection (GTR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.09 \u0026times; 10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.10 \u0026times; 10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubtotal / partial resection (STR/partial)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00 \u0026times; 10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtent of resection unspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.50 \u0026times; 10⁷\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRadiotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy given (yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24\u0026ndash;1.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.442\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDisease course\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.03\u0026ndash;8.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome category: neutral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.46\u0026ndash;36.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.207\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome category: unfavorable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.63\u0026ndash;52.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.122\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome category: unknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.32\u0026ndash;22.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.363\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.29\u0026ndash;2.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.828\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExtent of resection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGross total resection (GTR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.09 \u0026times; 10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.10 \u0026times; 10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubtotal / partial resection (STR/partial)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00 \u0026times; 10⁸\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtent of resection unspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.50 \u0026times; 10⁷\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 \u0026ndash; \u0026infin;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRadiotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy given (yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24\u0026ndash;1.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.442\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.03\u0026ndash;8.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDisease course\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.46\u0026ndash;36.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.207\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnfavourable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.63\u0026ndash;52.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.122\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.32\u0026ndash;22.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.363\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e* Statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eAcross the cohort, 36.6% of patients died and 19.5% experienced recurrence, with outcomes categorized as favorable, neutral, unfavorable, or unknown. In Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e, several covariates reached statistical significance, including markedly elevated hazard ratios for intraventricular 4th-ventricular tumours (HR 1.50 \u0026times; 10⁸), pineal region tumours (2.84 \u0026times; 10⁸), posterior fossa lesions (44.13), and lateralized lesions compared with midline, as well as protective effects for germ cell and glial tumours. Recurrence, GFAP positivity, and SALL4 expression were also significantly associated with poorer outcomes. BLUP-derived risk ratio estimates (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) ranged widely and often crossed the null, indicating considerable uncertainty. The Kaplan\u0026ndash;Meier curve (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) showed an early sharp drop in survival during the first year, followed by a relative plateau, with 5-year overall survival remaining slightly above 50%; the median survival was not reached, and confidence intervals widened substantially beyond 24 months due to decreasing numbers at risk.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eMolecular and Immunohistochemical Findings\u003c/h2\u003e \u003cp\u003eMolecular analysis, when available, consistently confirmed trisomy 21 across informative cases, with additional alterations spanning KRAS, PMS2, PTCH1, NF2, SMARCB1, RELA fusion, and SHH or WNT subgroup assignments, though no recurrent secondary molecular driver emerged (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Immunohistochemical profiles aligned with expected tumour lineages\u0026mdash;PLAP/OCT4/SALL4/c-KIT in germ cell tumours; CD20/BCL6/MUM1 in lymphoma; GFAP/OLIG2 in glial tumours\u0026mdash;while proliferative markers such as Ki-67 and p53 positivity were variably expressed. These findings reflect a heterogeneous but biologically coherent molecular landscape consistent with the tumour types represented, further illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our pooled IPD, we found that brain tumors in people with Down syndrome cluster in deep and midline structures, especially the basal ganglia/thalamus, pineal region, and posterior fossa vermis/4th ventricle, and that these locations are over-represented among germ cell tumors, embryonal tumors and gliomas. This pattern broadly supports prior reports that intracranial germ cell tumors preferentially arise in the pineal and suprasellar regions and that medulloblastoma and related embryonal tumors are typically posterior fossa/4th-ventricular lesions\u003csup\u003e46,47\u003c/sup\u003e, while also aligning with case reports of basal ganglia germinomas and deep-seated gliomas in Down syndrome. These sites are intimately related to CSF pathways, deep venous drainage, and the brainstem, so even modest tumor volumes can rapidly produce obstructive hydrocephalus, raised intracranial pressure and cranial neuropathies\u003csup\u003e48\u0026ndash;50\u003c/sup\u003e; this provides a plausible mechanistic explanation for the prominent motor, cerebellar and cranial nerve presentations, as well as for the substantial early mortality seen in our Kaplan\u0026ndash;Meier curve.\u003c/p\u003e \u003cp\u003eWith respect to survival, we found that tumor site and histology are the main statistically significant determinants of outcome, whereas most clinical comorbidities and presenting symptoms did not reach significance. Specifically, intraventricular 4th-ventricular tumors (HR 1.50\u0026times;10⁸, 95% CI 1.85\u0026times;10⁷\u0026ndash;1.22\u0026times;10⁹, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), pineal tumors (HR 2.84\u0026times;10⁸, 95% CI 5.83\u0026times;10⁷\u0026ndash;1.38\u0026times;10⁹, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and posterior fossa vermis/4th-ventricle lesions (HR 44.13, 95% CI 4.75\u0026ndash;409.98, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were associated with a markedly increased hazard of death, while germ cell tumors overall were associated with a substantially reduced hazard (HR 0.09, 95% CI 0.03\u0026ndash;0.28, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and glial tumors also showed a protective effect (HR 0.22, 95% CI 0.06\u0026ndash;0.80, p\u0026thinsp;=\u0026thinsp;0.022). These findings are broadly concordant with the general pediatric neuro-oncology literature, where germinomas and many non\u0026ndash;glioblastoma glial tumors are highly chemo radiosensitive with favorable long-term survival\u003csup\u003e51\u003c/sup\u003e, whereas 4th-ventricular embryonal tumors and high-grade gliomas carry a poor prognosis. This contrast reflects both tumor biology (e.g. intrinsic treatment sensitivity vs. infiltrative behaviour) and anatomy: pineal/4th-ventricular masses are harder to resect completely without brainstem or cerebellar injury\u003csup\u003e52\u003c/sup\u003e, and small residual disease in these compartments can have disproportionate clinical consequences.\u003c/p\u003e \u003cp\u003eAt the molecular and immunophenotypic level, our data suggest that only a few markers currently add statistically robust prognostic information, while most genetic alterations did not reach significance in this small cohort. SALL4 positivity, a marker of malignant germ cell components, was associated with a significantly increased hazard of death (HR 16.92, 95% CI 1.82\u0026ndash;157.60, p\u0026thinsp;=\u0026thinsp;0.013), and GFAP positivity was likewise linked to poorer survival (HR 5.33, 95% CI 1.09\u0026ndash;26.17, p\u0026thinsp;=\u0026thinsp;0.039), whereas other tested alterations (e.g. WNT/SHH subgrouping, KRAS/PMS2, NF2, SMARCB1) did not show clear prognostic effects. This partially supports existing evidence that, in Down syndrome, trisomy 21 is a constant background event while additional oncogenic drivers are heterogeneous rather than converging on a single dominant \u0026ldquo;\u003cem\u003esecond hit\u003c/em\u003e.\u0026rdquo; These patterns are consistent with the idea that brain tumors in Down syndrome arise from the same germ cell, glial, or embryonal lineages as in euploid patients\u003csup\u003e53,54\u003c/sup\u003e, but on a chromosomal-21\u0026ndash;enriched background that may subtly modulate tumor microenvironment, immune surveillance, and DNA damage responses without fully redefining lineage-specific behavior.\u003c/p\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eClinical Applicability\u003c/h2\u003e \u003cp\u003eEven though all included studies were case reports or small case series, in such a rare population this pooled individual patient data meta-analysis currently represents the most robust evidence base available to guide clinical decision-making. The synthesis shows that tumor type and anatomical site strongly shape presentation and survival, whereas traditional comorbidities (cardiac, endocrine, immune) are less clearly prognostic. This means that new focal neurological deficits, symptoms of raised intracranial pressure, or neuroendocrine changes in individuals with Down syndrome should trigger prompt, targeted neuroimaging of high-risk regions, and that deep midline germ cell tumours or glial tumours may warrant aggressive but carefully tailored multimodal therapy, while intraventricular and posterior fossa vermian lesions should be managed as particularly high-risk entities.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eStudy Limitaiton\u003c/h2\u003e \u003cp\u003eThis work is constrained by the fact that all included primary reports are case reports or case series, which are intrinsically prone to selection and publication bias toward atypical or severe presentations and limit control for confounding. The small sample size within many strata, together with sparse events, led to unstable hazard ratio estimates in the IPD meta-analysis, with several parameters yielding extreme values and confidence intervals extending from 0 to infinity, reflecting quasi-complete separation rather than true biological effects\u003csup\u003e55\u003c/sup\u003e. Heterogeneity in diagnostic era, imaging, histopathological classification, molecular testing, and treatment protocols, as well as incomplete and variably reported follow-up, further restricts the precision and generalizability of these findings.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe following IPD meta-analysis highlights a distinctive but heterogeneous landscape of brain tumours in people with Down syndrome, characterised by a predominance of deep and midline lesions, an over-representation of germ cell tumours, medulloblastoma and high-grade gliomas, and survival that is strongly influenced by anatomical location, histology and recurrence rather than by baseline comorbidities alone. While some entities appear to retain relatively favourable outcomes, intraventricular, pineal and posterior fossa vermian lesions carry a markedly increased hazard of death despite intensive therapy. These findings support a tailored, anatomy- and histology-guided approach to diagnosis and treatment in Down syndrome, and they underscore the need for prospective, registry-based collaborative studies to refine risk stratification, optimise neurosurgical and oncological strategies, and better define long-term functional outcomes in this vulnerable group.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAll of the authors declare that they have all participated in the design, execution, and analysis of the paper, and that they have approved the final version. Additionally, the material described is not under publication or consideration for publication elsewhere. \u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eEthical Statement: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eConsent: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur article does not require patient consent.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCompeting Interest: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funds were granted for this paper.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s Contribution:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eY.F.A conceptualized the study, finalized the topic, perform screening, major contribution to manuscript writing, drafting, literature search, discussion writing and provided overall supervision. J.H.W cleaned the data, carried out analysis, compiled the results, and compiled the manuscript. D.K carried out data extraction and quality assessment. M.Q.A carried out data extraction and quality assessment. R.N.S contributed to manuscript writing. K.A and S.H contributed to manuscript writing. \u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable \u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e: not applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMedline Plus. Down syndrome: MedlinePlus Genetics [Internet]. medlineplus.gov. 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Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/40705493/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/40705493/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Down Syndrome, Brain neoplasms, Trisomy 21, Survival outcomes, Mortality","lastPublishedDoi":"10.21203/rs.3.rs-8168623/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8168623/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eBrain tumours in individuals with Down syndrome (DS) are extremely rare, and little is known about their types, locations, molecular features, or outcomes. While DS is associated with a high risk of leukemia, solid tumours\u0026mdash;including those of the central nervous system\u0026mdash;appear unusually uncommon.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We performed a systematic review and individual patient data meta-analysis of published cases of brain tumours in DS, following PRISMA guidelines. Searches of PubMed, Scopus, and Web of Science up to 2025 identified studies reporting clinical, histological, treatment, or outcome data. Data on demographics, tumour characteristics, molecular markers, therapies, and survival were extracted and analyzed using descriptive statistics, survival analysis, and risk modeling.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 41 patients (mean age 13.6 years), most were pediatric (70.7%) and male (85.4%). Germ cell tumors predominated (46.3%), mainly in the basal ganglia/thalamus and pineal regions. All informative molecular tests confirmed trisomy 21 with diverse secondary alterations but no recurrent \u0026ldquo;second hit.\u0026rdquo; Intraventricular and pineal tumors showed significantly higher mortality risk (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), while germ cell (HR 0.09, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and glial tumors (HR 0.22, p\u0026thinsp;=\u0026thinsp;0.022) were associated with better outcomes. SALL4 (HR 16.9, p\u0026thinsp;=\u0026thinsp;0.013) and GFAP positivity (HR 5.3, p\u0026thinsp;=\u0026thinsp;0.039) predicted worse survival. Recurrence increased mortality risk (HR 2.98, p\u0026thinsp;=\u0026thinsp;0.044). Overall survival plateaued above 50% at 5 years, with no median survival reached.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eBrain tumours in DS show a distinct pattern, clustering in deep and midline structures and dominated by germ cell tumours, medulloblastomas, and high-grade gliomas. Outcomes depend primarily on tumour location and type rather than underlying comorbidities. These findings emphasize the need for careful, tailored management and highlight the importance of collaborative studies to improve understanding and treatment strategies in this vulnerable population.\u003c/p\u003e","manuscriptTitle":"Brain Tumours in Individuals with Down Syndrome: An Individual Patient Data Meta-analysis of Incidence, Patterns and Outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-18 10:12:21","doi":"10.21203/rs.3.rs-8168623/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c22fbcd5-a059-44d8-80ea-fb25049279b0","owner":[],"postedDate":"March 18th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-18T10:12:39+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-18 10:12:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8168623","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8168623","identity":"rs-8168623","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}