Integrating molecular markers into the World Health Organization classification of CNS tumors: a survey of the neuro-oncology community

Abstract

Background: Molecular markers provide important biological and clinical information related to the classification of brain tumors, and the integration of relevant molecular parameters into brain tumor classification systems has been a widely discussed topic in neuro-oncology over the past decade. With recent advances in the development of clinically relevant molecular signatures and the 2016 World Health Organization (WHO) update, the views of the neuro-oncology community on such changes would be informative for implementing this process.

Methods: A survey with 8 questions regarding molecular markers in tumor classification was sent to an email list of Society for Neuro-Oncology members and attendees of prior meetings (n=5065). There were 403 respondents. Analysis was performed using whole group response, based on self-reported subspecialty.

Results: The survey results show overall strong support for incorporating molecular knowledge into the classification and clinical management of brain tumors. Across all 7 subspecialty groups, ≥70% of respondents agreed to this integration. Interestingly, some variability is seen among subspecialties, notably with lowest support from neuropathologists, which may reflect their roles in implementing such diagnostic technologies.

Conclusion: Based on a survey provided to the neuro-oncology community, we report strong support for the integration of molecular markers into the WHO classification of brain tumors, as well as for using an integrated "layered" diagnostic format. While membership from each specialty showed support, there was variation by specialty in enthusiasm regarding proposed changes. The initial results of this survey influenced the deliberations underlying the 2016 WHO classification of tumors of the central nervous system.

Keywords: classification; molecular markers; pathology.

Fig. 1.

Responses to the survey divided into whole group response (left) and response according to self-identified subspecialty (right). Responses within each subspecialty were compared with responses of the remainder of the respondents and noted with an asterix if significantly different (P<.05 by either chi-square or Fisher’s exact test). (A) Responses to whether knowledge of molecular classification of brain tumors is at a level where it can be integrated into the WHO classification system (n=403). (B) Responses to address how important the incorporation of 1p/19q testing into the classification system is for patient management of grade III gliomas (n=396). (C) Responses to whether IDH mutation testing is as important in determining treatment and/or management decisions for patients with diffuse glioma (n=402).

Fig. 2.

(A) Responses to whether treatment should change the overall management and approach of grade III AA IDH-wt vs IDH-mut tumors (n=394). (B) Responses addressing whether the treatment and overall management of GBM should be affected based on IDH mutation status (n=392). (C) Responses to whether pediatric gliomas should be classified differently than their histologically similar adult counterparts due to their distinct molecular profile (n=398).

Fig. 3.

(A) Responses to whether approach and management of elderly patients should change patients if the results of MGMT testing were included in the classification of GBM (n=397). (B) Responses to what the neuro-oncology community thinks of the proposed integrated diagnosis and the summary description of the recent meeting to plan the next update of the WHO classification (n=381).