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EANO Guidelines on the Diagnosis and Treatment of Diffuse Gliomas of Adulthood

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EANO Guidelines on the Diagnosis and Treatment of Diffuse Gliomas of Adulthood EVIDENCE-BASED GUIDELINES OPEN EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood Michael Weller1 ✉ , Martin van den Bent 2, Matthias Preusser 3, Emilie Le Rhun4,5,6,7, Jörg C. Tonn8, Giuseppe Minniti 9, Martin Bendszus10, Carmen Balana 11, Olivier Chinot12, Linda Dirven13,14, Pim French 15, Monika E. Hegi 16, Asgeir S. Jakola 17,18, Michael Platten19,20, Patrick Roth1, Roberta Rudà21, Susan Short 22, Marion Smits 23, Martin J. B. Taphoorn13,14, Andreas von Deimling24,25, Manfred Westphal26, Riccardo Soffietti 21, Guido Reifenberger27,28 and Wolfgang Wick 29,30 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. The classification of gliomas has undergone major such as differential diagnosis, adverse effects of treat- changes through the revision of the fourth edition of the ment, and supportive and palliative care are beyond the WHO Classification of Tumors of the Central Nervous scope of this guideline document. System1 in 2016. Further refinements of the classifica- tion were subsequently proposed by the Consortium Methods to Inform Molecular and Practical Approaches to These evidence- based guidelines were formulated by CNS Tumour Taxonomy — Not Officially WHO a task force nominated by the EANO Executive Board (cIMPACT- NOW)2–4. These documents enable a diag- following a proposal by the Chair of the EANO guide- nosis of glioblastoma to be made not only based on lines committee. This task force includes representa- histology but also on the basis of several molecular tives of all the disciplines involved in the diagnosis and markers and propose the discontinuation of the term care of adults with glioma and reflects the multinational ‘IDH- mutant glioblastoma’. To reflect these changes, character of EANO. References were retrieved from the the European Association of Neuro- Oncology (EANO) PubMed database using the search terms ‘glioma’, ‘ana- considered it necessary to update its guidelines for the plastic’, ‘astrocytoma’, ‘oligodendroglioma’, ‘glioblastoma’, management of adult patients with gliomas5 (BOx 1). In ‘trial’, ‘clinical’, ‘surgery’, ‘radiotherapy’ and ‘chemother- ✉e- mail: michael.weller@ the present evidence- based guidelines, we cover the apy’ between January 2011 and July 2020. Publications usz.ch prevention, early diagnosis and screening, integrated were also identified through searches of the authors’ own https://doi.org/10.1038/ histo molecular diagnostics, therapy and follow-up mon- libraries. Only publications in English were reviewed. s41571-020-00447- z itoring of adult patients with diffuse gliomas. Aspects Data available only in abstract form were included in 170 | MARCH 2021 | VOLUME 18 www.nature.com/nrclinonc EVIDENCE-BASED GUIDELINES exceptional circumstances. The definitive reference list tuberous sclerosis, Turcot syndrome, Li–Fraumeni was generated based on relevance to the broad scope of syndrome and Lynch syndrome. Screening with neuro- these guidelines. The consensus recommendations were imaging is limited to patients with such syndromes at achieved through repeated circulation of manuscript the initial diagnostic work- up8. Repeat neuroimaging drafts and telephone conferences involving members of is not indicated unless new neurological symptoms and the task force to discuss the most controversial areas. signs, such a seizures, aphasia, hemiparesis or sensory The key recommendations for the diagnosis and man- deficits, develop that suggest an intracranial lesion. The agement of diffuse gliomas of adulthood, with their class counselling and screening of asymptomatic relatives of evidence (C) and level of recommendation (L)6 are of patients with glioma who are found to be carriers of reported at the end of each corresponding paragraph. germline mutations associated with gliomagenesis should be conducted with caution and in cooperation Epidemiology and prevention with clinical geneticists. No known measures to prevent The annual incidence of gliomas is approximately of the development of gliomas exist. six cases per 100,000 individuals worldwide. Men are 1.6- fold more likely to be diagnosed with gliomas than History and clinical examination women7. While the vast majority of cases are sporadic, The evolution of neurological symptoms and signs certain familial tumour syndromes are associated with enables the estimation of the growth dynamics of glio- gliomagenesis, including neurofibromatosis type I, mas: tumours that cause symptoms only weeks before diagnosis are usually fast growing whereas those that cause symptoms for years before being diagnosed are Author addresses usually slow growing. In most individuals, the symp- 1Department of Neurology, Clinical Neuroscience Center, University Hospital and toms and signs reported the year before diagnosis are University of Zurich, Zurich, Switzerland. non- specific (for example, fatigue or headache)9–11. 2 Brain Tumor Center at Erasmus MC Cancer Institute, University Medical Center A discussion of the patient’s history might reveal famil- Rotterdam, Rotterdam, Netherlands. ial risk or rare exogenous risk factors (such as exposure 3Division of Oncology, Department of Medicine I, Medical University of Vienna, to radiation) associated with the development of brain Vienna, Austria. 4Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and tumours. Information from relatives might be required University of Zurich, Zurich, Switzerland. to obtain a reliable history. Firm recommendations on 5University of Lille, U1192, Lille, France. when and how to involve family members and caregiv- 6Centre Hospitalier Universitaire (CHU) Lille, Neuro-​Oncology, General and Stereotaxic ers and how to assess the medical decision- making Neurosurgery Service, Lille, France. capacity in patients with brain tumours remain to be 7Oscar Lambret Center, Neurology, Lille, France. developed12. 8Department of Neurosurgery, University Hospital Munich LMU, Munich, Germany. Characteristic modes of clinical presentation include 9 Radiation Oncology Unit, Department of Medicine, Surgery and Neurosciences, new- onset epilepsy, focal deficits (such as pareses or University of Siena, Siena, Italy. sensory disturbances), neurocognitive impairment, and 10Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany. symptoms and signs of increased intracranial pressure. 11Catalan Institute of Oncology (ICO), Hospital Germans Trias i Pujol, Badalona, Spain. 12Aix- Marseille Université, Assistance Publique–Hôpitaux de Marseille (APHM), CHU The physical examination of patients with brain tumours Timone, Department of Neuro-​Oncology, Marseille, France. focuses on the detection of systemic cancer to differen- 13Department of Neurology, Leiden University Medical Center, Leiden, Netherlands. tiate primary brain tumours from brain metastases and 14Department of Neurology, Haaglanden Medical Center, The Hague, Netherlands. contraindications for neurosurgical procedures. The 15Department of Neurology, Erasmus MC, Rotterdam, Netherlands. Neurological Assessment in Neuro- Oncology (NANO) 16Department of Clinical Neurosciences, University Hospital Lausanne, Lausanne, scale can be used to document some of the results of the Switzerland. neurological examination13. Neurocognitive assessment 17 Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden. using a standardized test battery14, beyond documenting 18 Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, performance status and performing a Mini Mental State Sahlgrenska Academy, Gothenburg, Sweden. 15 19 Examination (MMSE) or a Montreal Cognitive Assess- Department of Neurology, Medical Faculty Mannheim, Mannheim Center for 16 Translational Neuroscience (MCTN), Heidelberg University, Mannheim, Germany. ment (MoCA) , has become increasingly common. 20German Consortium of Translational Cancer Research (DKTK), Clinical Cooperation Despite its limitations, the MMSE is widely used as a Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center screening instrument to detect neurocognitive impairment (DKFZ), Heidelberg, Germany. and remains freely available for individual use. 21Department
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