UNITE  towards clinical implementation

In response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy – Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers.

 

LINK TO PUBLICATION

Weller M, van den Bent M, Preusser M, Le Rhun E, Tonn JC, Minniti G, Bendszus M*, Balana C, Chinot O, Dirven L, French P, Hegi ME, Jakola AS, Platten M*, Roth P, Rudà R, Short S, Smits M, Taphoorn MJB, von Deimling A*, Westphal M, Soffietti R, Reifenberger G, Wick W*. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2020 Dec 8. doi: 10.1038/s41571-020-00447-z. Online ahead of print.Nat Rev Clin Oncol. 2020.PMID: 33293629

*UNITE Principle Investigators

Research findings related to UNITE work package B01

Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, Michael Platten et al. investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. They made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. They provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and T_reg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB.

LINK TO PUBLICATION

Aslan K, Turco V, Blobner J, Sonner JK, Liuzzi AR, Núñez NG, De Feo D, Kickingereder P*, Fischer M, Green E, Sadik A, Friedrich M, Sanghvi K, Kilian M, Cichon F, Wolf L, Jähne K, von Landenberg A, Bunse L*, Sahm F*, Schrimpf D, Meyer J, Alexander A, Brugnara G, Röth R, Pfleiderer K, Niesler B, von Deimling A, Opitz C, Breckwoldt MO, Heiland S, Bendszus M*, Wick W*, Becher B, Platten M*. Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas. Nat Commun. 2020 Feb 18;11(1):931. *UNITE Principle Investigators