Letter regarding Louis et al: The 2021 WHO Classification of Tumors of the Central Nervous System: A summary

One of the aims of the “2021 WHO Classification of Tumours of the Central Nervous System (CNS)” is to provide practical guidance to pathologists and neuro-oncology specialists around the world in order to benefit patients with CNS tumors.1 This “international standard” incorporates numerous molecular changes with clinicopathologic utility that are important for the most accurate classification of CNS neoplasms, alongside describing new tumor types using novel diagnostic technologies such as DNA methylome profiling.1 We aim to address the key issues that are applicable to the Global Neuro-oncological community, particularly in low- and middle-income countries (LMICs). This global classification, based on such advanced techniques, has limited benefit for resource-challenged LMICs. Significant heterogeneity prevails in the practice of neuro-oncology, even within countries that have established evidence-based guidelines.2 With the increase in complexity of molecular diagnosis, neuropathologists are needed to analyze samples and tailor specific therapeutic regimens. The lack of trained pathologists and availability of immunohistochemistry (IHC), alongside a scarcity of neuro-oncologists, are major contributors to the misdiagnosis of CNS cancers in LMICs.2 Therefore, it is unlikely that this “global” classification system would be of significant benefit to the majority of patients in LMICs. This is reinforced when examining adjuvant temozolomide as a superior glioblastoma treatment; it is cost-effective in high-income countries (HICs) but not in LMICs such as India. Interestingly, this study found that a 90% reduction in price of Temozolamide is likely to increase its cost-effectiveness to 80%.3 One may question how LMICs would fully benefit from such an elaborate scientific classification system when they have limited access to basic cost-effective treatments. Neuro-oncology is a new subspecialty to many LMICs, with some not recognizing it at all,2 despite the fact that most children with CNS tumors are diagnosed in LMICs. Health systems are not frequently equipped to manage complex cases.2 The UK’s NICE recommends the 2016 WHO classification of CNS tumors for glioma classification, including the use of molecular markers and standard histopathology, such as IDH and ATRX, as well as 1p/19q testing.4 This comes with additional cost and higher turnaround time, which is not practical in LMICs. Therefore, the Indian Society for Neuro-Oncology (ISNO) has altered these guidelines to be more practical for India; whilst IHC for IDH1, ATRX, and P53 are available in most laboratories, fluorescence in situ hybridization (FISH) and DNA sequencing for 1p/19q testing is offered mostly in major centers. The ISNO guidelines involve the use of ATRX and IDH mutations for classification of adult diffuse gliomas, with no need for 1p/19q testing, allowing the multidisciplinary team to arrive at a diagnosis with the minimum number of molecular tests, helping to decide an appropriate management strategy.5 Hence, the statement that the WHO CNS Tumour classification can benefit people around the world perhaps should be used judiciously. In LMICs, guidelines rely on accurate diagnosis, available surgical expertise, and treatment proximity, availability, and affordability.5 The introduction of an evidence-based global classification of CNS Tumours that echoes the ISNO guidelines, would be more beneficial in a resource-limited setting. There remains a lower availability of disease-specific guidelines in LMICs, despite uniform guidelines contributing largely to improved patient outcomes.6 In a study conducted in Paraguay, it was found that there needs to be an effort to develop guidelines for the more common pediatric brain tumors based on available resources, treatment toxicities, timing of initiation of radiotherapy, and prudent use of limited imaging resources, such as MRI.6 Perhaps a greater representation of authors from LMICs would be beneficial to derive specific guidelines for LMICs in collaboration with authors in HICs, facilitating input from multiple physicians and improving outcomes. None. Conflict of interest statement. The authors declare no conflict of interest.