Globalising the access to advanced molecular diagnostics of CNS tumors: Experience of the Molecular Neuro-Pathology (MNP) Outreach Consortium

Abstract

Central nervous system (CNS) tumors pose a major global health challenge, particularly in low- and middle-income countries (LMICs), where outcomes remain disproportionately poor. The global CONCORD-3 study (Lancet Oncology) highlighted stark disparities in five-year survival (2010-2014): from ∼15% in Thailand to 46% in Japan among adults, and from ∼ 80% in Denmark to < 40% in Brazil among children. Limited access to specialized pathology and molecular diagnostics in LMICs results in diagnostic uncertainty and restricted treatment options. DNA methylation-based tumor classification, has revolutionized CNS tumor diagnosis and got incorporated into the 2021 world health organization (WHO) CNS5 classification. However, its accessibility, feasibility, and performance in LMICs remain insufficiently explored. Importantly, several ethnic groups common in LMICs are underrepresented in current reference datasets. To address this, the Molecular Neuro-Pathology (MNP) Outreach Consortium was launched in Heidelberg, partnering with 11 countries-including nine LMICs from Asia, Africa, and South America. Early insights from Brazil, Jordan and Argentina, show methylation profiling changing diagnosis in up to 25% cases. Gains are greatest in pediatric and adolescents and young adults (AYA) populations. In addition, it reduced the designation of not otherwise specified (NOS) from 51.3% to 8.8% across 476 CNS tumours in Brazil.