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Introduction: Advancements in genomic profiling led to the discovery of four major molecular subgroups in medulloblastoma (MB), which have now been incorporated into the World Health Organization classification of central nervous system tumors. The current study aimed to determine the prognostic significance of the MB molecular subgroups among children in Malaysia. Methods: We assembled MB samples from children <18 years between January 2003 and June 2017 from four pediatric oncology centers in Malaysia. MB was sub-grouped using 850k DNA methylation testing at German Cancer Research Centre, Heidelberg, Germany. Results: Fifty samples from patients diagnosed and treated as MB were identified. Two (4%) of the 50 patients' tumor DNA sampleswere insufficient for analysis. Of the remaining 48 patients, 41 (85%) samples were confirmed as MB, while for 7 (15%) patients, DNA methylation classification results were discrepant with the histopathological diagnosis of MB, with various other diagnoses. Of the 41 MB patients, 15 patients were stratified as standard-risk (SR), 16 patients as high-risk (HR), and ten as infants (age <3 years old). Molecular subgrouping of the whole cohort revealed four (14%) WNT, 11 (27%) SHH, 10 (24%) Group 3, and 16 (39%) Group 4. Treatment abandonment rates for older children and infants were 22.5% and 10%, respectively. After censoring treatment abandonment, for SR patients, the 5-year event-free survival (EFS) and overall survival (OS) were 43.1% ± 14.7% and 46.9 ± 15.6%, respectively, while in HR, 5-year EFS andOS were both 63.6% ± 14.5%. Infants had a 5-year EFS and OS of 55.6% ± 16.6% and 66.7% ± 15.7%, respectively. WNT tumors had the best 5y-OS, followed by Group 3, Group 4, and SHH in children =3 years old. In younger children, SHH MB patients showed favorable outcomes. Conclusion: The study highlights the importance of DNA methylation profiling for diagnostic accuracy. Most infants had SHH MB, and their EFS and OS were comparable to those reported in high-income countries. Due to the relatively small cohort and the high treatment abandonment rate, definite conclusions cannot be made regarding the prognostic significance of molecular subgroups of MB. Implementing this high-technology investigation would assist pathologists in improving the diagnosis and provide molecular subgrouping of MB, permitting subgroup-specific therapies. [ABSTRACT FROM AUTHOR]

Pediatric central nervous system tumor survivors (CNSTS) experience late effects that may affect their health-related quality of life (HRQOL). The study aims: i) compare HRQOL among Malaysian CNSTS with acute lymphoblastic leukemia survivors (ALLS) and healthy children, and ii) explore factors associated with low HRQOL. We performed a comparative cross-sectional HRQOL study of 46 CNSTS aged 5-18 years and 90 ALLS (age and gender-matched) who completed treatment for >1 year, and a published cohort of healthy children. Pediatric Quality of Life Inventory (PedsQL) was used for all groups and PedsQL Cancer Module for CNSTS and ALLS. Multiple regression analysis was used to determine factors associated with low HRQOL. Mean PedsQL total scale score, physical health score and psychosocial health score of CNSTS were 69.0 (SD 20.3), 68.7 (SD 27.9) and 69.2 (SD 19.2) respectively. These scores were significantly lower in all domains particularly in teenagers compared with healthy children and ALLS. The median PedsQL Cancer Module score of CNSTS was significantly lower than ALLS in total scale, cognitive problems and communication. Physical impairment was associated with lower PedsQL scores in all 3 domains; special education placement was associated with lower PedsQL total scale and physical health scores and clinically significant internalizing behavioral difficulties score was associated with lower PedsQL psychosocial health scores. CNSTS reported lower PedsQL scores in all domains than ALLS and healthy children. Clinicians need to be vigilant of HRQOL needs among CNSTS, especially those with risk factors of special education needs, physical impairment, and internalizing behavioral difficulties. [ABSTRACT FROM AUTHOR]

Purpose: Multidisciplinary team meetings (MDTMs) are essential in the clinical management of pediatric central nervous system (CNS) tumors. Evaluations of the impact of MDTMs on childhood CNS tumors and clinicians' perspectives on their effectiveness are scarce. Methods: We retrospectively reviewed the clinical data of pediatric patients (aged <18 years) with CNS tumors diagnosed and treated in the Pediatric Hematology-Oncology Division at the University Malaya Medical Center from 2008 to 2019. We also conducted a web-based survey of the core members of the multidisciplinary team to evaluate the impact of the MDTMs. Results: During the pre-MDTM era (2008–2012), 29 CNS tumors were diagnosed and treated, and during the MDTM era (2014–2019), 49 CNS tumors were diagnosed and treated. The interval for histologic diagnosis was significantly shorter during the MDTM era (p=0.04), but the interval from diagnosis to chemotherapy or radiotherapy and the 5-year overall survival of the 78 patients did not improve (62.1% ± 9.0% vs. 68.8% ± 9.1%; p=0.184). However, the 5-year overall survival of patients with medulloblastoma or rare tumors significantly improved in the MDTM era (p=0.01). Key factors that contributed to delayed treatment and poor outcomes were postoperative complications, the facility's lack of infrastructure, poor parental education about early treatment, cultural beliefs in alternative medicine, and infection during chemotherapy. Eighteen clinicians responded to the survey; they felt that the MDTMs were beneficial in decision-making and enhanced the continuity of coordinated care. Conclusion: MDTMs significantly reduced the diagnostic interval and improved the overall outcomes. However, delayed treatment remains a major challenge that requires further attention. [ABSTRACT FROM AUTHOR]