Prognostic Importance of Histomolecular Subtyping of Central Nervous System Gliomas in Low and Middle-Income Countries

Background Access to advanced histomolecular diagnostic testing for central nervous system (CNS) tumors is limited in low and middle-income countries (LMICs), hindering adequate characterization and failure to reach a WHO CNS 2021 diagnosis. LMICs also lack access to targeted therapies, and even conventional chemotherapy and radiation therapies vary between LMICs and high-income countries. Consequently, whether histomolecular subclassification is clinically beneficial and if it provides prognostic information in an LMIC setting is not clear. Here, we address this question by presenting the first systematic prospective study of CNS glioma patients from Pakistan, examining differences in overall survival (OS) by histomolecular subtype. Methods A total of 194 patients with CNS tumors were enrolled at a single tertiary-care center in Karachi, Pakistan. Routine histochemical processing, immunohistochemistry, and molecular testing using fluorescence in situ hybridization analysis, limited targeted-panel next-generation sequencing, and polymerase chain reaction were performed to test for isocitrate dehydrogenase (IDH) 1 and 2, P53, ATRX, Ki-67, 1p/19q co-deletion, and MGMT promoter methylation. Results The results revealed that IDH status was a significant independent prognostic factor, regardless of age (p=0.016), with a 1-year survival rate of 76% and median OS of 16.15 months in IDH-wildtype high-grade gliomas. Conversely, the 1-year survival rate was 95% for IDH-mutant gliomas. Significant survival differences were observed for ATRX status (retained vs. loss) in IDH-mutant gliomas (p=0.046), P53 mutations in IDH-wildtype high-grade gliomas (p=0.05), and 1p/19q co-deletion in grade 3 gliomas (log-rank p=0.023). Conclusion We provide empirical evidence supporting a role for histo-morphological and limited molecular testing in neuro-oncology practice in LMICs.