EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood

Michael Weller, Martin van den Bent, Matthias Preusser, Emilie Le Rhun, Jörg C Tonn, Giuseppe Minniti, Martin Bendszus, Carmen Balana, Olivier Chinot, Linda Dirven, Pim French, Monika E Hegi, Asgeir S Jakola, Michael Platten, Patrick Roth, Roberta Rudà, Susan Short, Marion Smits, Martin J B Taphoorn, Andreas von Deimling, Manfred Westphal, Riccardo Soffietti, Guido Reifenberger, Wolfgang Wick, Michael Weller, Martin van den Bent, Matthias Preusser, Emilie Le Rhun, Jörg C Tonn, Giuseppe Minniti, Martin Bendszus, Carmen Balana, Olivier Chinot, Linda Dirven, Pim French, Monika E Hegi, Asgeir S Jakola, Michael Platten, Patrick Roth, Roberta Rudà, Susan Short, Marion Smits, Martin J B Taphoorn, Andreas von Deimling, Manfred Westphal, Riccardo Soffietti, Guido Reifenberger, Wolfgang Wick

Abstract

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.

Conflict of interest statement

M.W. reports grants and personal fees from Abbvie, Merck (EMD) and MSD, grants from Adastra, Dracen and Novocure, personal fees from Basilea, BMS, Celgene, Medac, Nerviano Medical Sciences, Orbus, Roche and Tocagen. M.vdB. reports personal fees from Abbvie, Agios, Bayer, Carthera, Genenta, Karyopharm and Nerviano Medical Sciences. M.Preusser reports grants and personal fees from Abbvie, Daiichi Sankyo, GlaxoSmithKline and MSD, grants from Böhringer Ingelheim, Bristol Myers Squibb, Novocure and Roche, and personal fees from AstraZeneca, Bayer, BMJ Journals, BMS, CMC Contrast, Gerson Lehrman Group, Lilly, Medahead, MedMedia, Mundipharma, Novartis, Roche, Sanofi and Tocagen. E.L.R. reports personal fees from Abbvie, Daiichy Sankyo and Tocagen. J.C.T. reports personal fees from BrainLab and Carthera. M.B. reports grants and personal fees from Novartis, grants from Siemens, and personal fees from B. Braun, Bayer, Boehringer Ingelheim, Grifols, Merck, Springer, Teva and Vascular Dynamics. C.B. reports personal fees from Celgene, Karyopharm, Lipopharma and Pharmamar, and other support from Abbvie. O.C. reports personal fees and travel support from Abbvie. M.E.H. reports funding from Bristol Myers Squibb and Novocure. A.S.J. reports personal fees from INOMED. M.Pl. reports non-financial support from Pfizer and Roche, personal fees and supply of reagents from Bayer, and personal fees from Affiris, Apogenix and Novartis. In addition, M.Pl has six patents licensed to Bayer (EP2753315B1, WO2018146010A1, WO2019101643A1, WO2019101647A1, WO2019101641A1 and WO2019101642A1), one patent issued (EP2800580B1) and three patents pending (US20180155403A1, US20180246118A1 and US20170254803A1). P.R. reports grants and personal fees from Novocure and personal fees from Bristol Myers Squibb, Debiopharm, Medac, Merck, MSD, QED and Roche. S.S. reports personal fees from Hox Therapeutics and Tocagen and personal fees and support of reagents from Abbvie. M.S. reports other support from GE Healthcare and Parexel. A.vD. receives royalties for the diagnostic use of IDH1 R132H mutant-specific antibody H09; all terms are being managed by the German Cancer Research Center in accordance with its conflict of interest policies. R.S. reports personal fees from AstraZeneca, EISAI, Merck and Puma Biotechnologies. G.R. reports personal fees from Abbvie. G.M., L.D., P.F., R.R., M.J.B.T., M.W. and W.W. declare no competing interests.

Figures

Fig. 1. Diagnostic algorithm for the integrated…
Fig. 1. Diagnostic algorithm for the integrated classification of the major diffuse gliomas in adults.
Tissue specimens obtained through biopsy sampling in patients with diffuse gliomas are routinely assessed by immunohistochemistry for the presence of R132H-mutant IDH1 and loss of nuclear ATRX. In patients aged >55 years with a histologically typical glioblastoma, without a pre-existing lower grade glioma, with a non-midline tumour location and with retained nuclear ATRX expression, immunohistochemical negativity for IDH1 R132H suffices for the classification as IDH-wild-type glioblastoma. In all other instances of diffuse gliomas, a lack of IDH1 R132H immunopositivity should be followed by IDH1 and IDH2 DNA sequencing to detect or exclude the presence of non-canonical mutations. IDH-wild-type diffuse astrocytic gliomas without microvascular proliferation or necrosis should be tested for EGFR amplification, TERT promoter mutation and a +7/–10 cytogenetic signature as molecular characteristics of IDH-wild-type glioblastomas. In addition, the presence of histone H3.3 G34R/V mutations should be assessed by immunohistochemistry or DNA sequencing to identify H3.3 G34-mutant diffuse hemispheric gliomas, in particular in young patients with IDH-wild-type gliomas (such as those <50 years of age with nuclear ATRX loss in tumour cells). Diffuse gliomas of the thalamus, brainstem or spinal cord should be evaluated for histone H3 K27M mutations and loss of nuclear K27-trimethylated histone H3 (H3K27me3) to identify H3 K27M-mutant diffuse midline gliomas. The presence and absence of the diagnostically most relevant molecular alterations for each tumour type are highlighted with red and green boxes. MVP, microvascular proliferation.
Fig. 2. Clinical pathway for IDH-mutant gliomas.
Fig. 2. Clinical pathway for IDH-mutant gliomas.
KPS, Karnofsky performance status; PCV, procarbazine, lomustine and vincristine.
Fig. 3. Clinical pathway for IDH-wild-type glioblastomas,…
Fig. 3. Clinical pathway for IDH-wild-type glioblastomas, WHO grade 4.
KPS, Karnofsky performance status.

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Source: PubMed

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