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025. Impact of Molecular Genetics on Survival in Pediatric Supratentorial Ependymomas: A Scoping Review

Authors: Manasa Pagadala

Introduction:
Supratentorial ependymoma is a location-specific subset of ependymomas of which multiple molecular subtypes have been characterized, most commonly C11orf95-RELA fusion-positive (RELA fusion) and YAP1-MAMLD1 fusion (Yap1 fusion), along with many others. We conducted a scoping literature review to identify molecular subtypes and their associated survival data to better predict prognostic outcomes.Methods: A scoping review was conducted to explore molecular subtypes and associated survival data of supratentorial ependymoma using Embase, Scopus, and PubMed databases. The papers yielded from these database searches were screened by abstract and full text review. Studies that met the inclusion criteria were extracted of their data and cited in this review.
Results:
Of 180 papers, 14 were included for data extraction. Pajtler et al. reported that RELA fusions (5-year PFS: 29%, 5-year OS: 75%) had the poorest outcomes in comparison to YAP1 fusions (5-year PFS: 66%, 5-year OS: 100%) and subependymomas (5-year PFS: 100%, 5-year OS: 100%). The presence of C11orf95-RELA gene fusion (median PFS: 8.1, median OS: 9.4) had better survival outcomes compared with C11orf95 rearrangement (median PFS: 3.3, median OS: 6.3). In Páges et al., YAP1-fused and ependymal/subependymal mixed tumors had 10-year OS and PFS of 100%, supporting a better outcome. Additionally, the presence of RELA fusions, L1CAM immunopositivity and MIB1 labelling were all associated with poorer PFS, according to Malgulwar et al. Homozygous and hemizygous deletion of CDKN2A both showed significant lower OS (p=0.034) compared to no deletion for RELA+ ependymomas.
Conclusion:
Our study has shown that fusion, deletion, and rearrangement of certain genes may affect the survival outcomes of supratentorial ependymomas in pediatric patients. Knowing molecular subtype can help target therapies and understand the prognosis better. Future studies are needed to standardize survival data to further understand the impact of molecular subtypes on the prognostic outcomes of supratentorial ependymomas.