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OBJECTIVE To determine the prognostic significance of the four molecular subgroups of medulloblastoma (MB) among children in Malaysia. METHODS We assembled MB samples of children < 18 years between January 1999 and July 2017 in University Malaya Medical Centre, Penang General Hospital, Sarawak General Hospital and Sabah Woman and Children’s Hospital. MB was sub-grouped using 850k DNA methylation profiling. RESULTS Fifty-one tumour samples were retrieved. Histopathological subtypes were classic (n=12), MB extensive nodularity/desmoplastic (n=9) and 30 MB results without subtypes. Thirteen patients were M1-M4. Fourteen patients were stratified as standard-risk (SR,27.4%), 22 as high-risk (HR,43.2%) and 15 as high-risk children ≤ 3 years old (iHR,29.4%). Molecular subgrouping revealed 16 Group4, 11 SHH, 10 Group3 and 4 Wnt. In 8 patients, DNA methylation profiling identified a diagnosis other than MB and in 2 samples the DNA was inadequate. For patients >3 years old, the 5-year event-free survival (EFS) was 35.7%±13% in HR and 39.7%±20% in SR. The 5-year overall survival (OS) in these two groups was 43.4%±14% and 41.7±30% respectively. iHR had 5-year EFS and OS of 48.0%±16% and 60.0%±16% respectively. WNT tumours had the best 5y-OS of 66.7±22% of the cohort, albeit significantly lower than other reports, followed by SHH (56.8±17%), Group4 (44.3±17.6%) and Group3 (41.7±18%). Treatment abandonment rate was 20%. CONCLUSION The discrepancy in the histological diagnoses highlights the importance of DNA methylation profiling technique for accurate diagnosis. We observed poor OS across all the subgroups, in part due to treatment abandonment.

OBJECTIVE: To evaluate the survival outcomes in patients diagnosed with intracranial germ cell tumours (iGCT). METHODS: Retrospective review of all patients with iGCT treated in a single center from July 1996 to Jun 2017. Three treatment regimens were used: MSKCC, SIOP CNS GCT 96 and SIOP CNS GCT II. RESULTS: Thirty patients were identified with a median follow-up of 4.04 years (range 0.17–19.10). The mean age was 10.23 years. Male: female ratio was 5:1. Visual impairment (50%), endocrinopathy (30%) and precocious puberty (20%) were the commonest presenting symptoms. Duration of symptoms prior to presentation ranged from 1 to 108 weeks. Pure germinomas (n=15) and non-germinomatous germ cell tumours (NGGCT) (n=15) were equally distributed. Tumour location was pineal in 15 (50.0%), suprasellar in 8 (26.7%), hypothalamic in 2 (6.7%) and other sites (basal ganglia, thalamus, frontal lobe) in 5 (16.7%) patients. Eight patients (26.7%) had metastatic disease at diagnosis. Four cases underwent surgical debulking, 14 were biopsied and 7 had complete resection. Fifteen patients received chemo-radiotherapy, 7 had chemotherapy only and 8 underwent radiotherapy only. Elevated levels of serum alpha-fetoprotein and beta-human chorionic gonadotropin normalised after 2 courses of chemotherapy in all NGGCT cases. The 5-year event-free survival (EFS) and overall survival (OS) were 61.3 ± 14.1% and 78.3 ± 11.1% for pure germinoma, respectively. For NGGCT, the 5-year EFS and OS were 36.0 ± 13.3% and 41.3 ± 13.7%. Eleven recurrences occurred within a median duration of 11 months following diagnosis and 8 of them died within 10 months. CONCLUSION: Compared to pure germinoma, NGGCTs have poor prognosis.