Prof. Matthias Preusser from the Medical University of Vienna discusses EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood.
Instract
The European Association of Neuro-Oncology (EANO) acknowledged the need to include revised recommendations for the diagnosis and treatment of adult patients with diffuse gliomas in response to significant developments in diagnostic algorithms and the publication of mature findings from numerous broad clinical trials. A task force of EANO offers guidance for the diagnosis, treatment, and follow-up of adult patients with diffuse gliomas through these evidence-based guidelines. The diagnostic portion is focused on the 2016 update of the WHO Central Nervous System Tumor Classification and the subsequent Consortium Guidelines for Informing Molecular and Functional Approaches to CNS Tumor Taxonomy (cIMPACT-NOW). With respect to treatment, we have developed guidelines based on the outcomes of recent clinical trials that have improved practice and offer guidance for neuropathological and neuroradiological evaluation as well. The position of the major treatment modalities of surgery, radiotherapy, and systemic pharmacotherapy is specified in these guidelines, covering current developments and recognizing that unnecessary procedures and expenses should be avoided. The aim of this document is to serve as a guide for clinicians involved in the treatment of diffuse glioma patients in adults, patients and caregivers, and health care providers.
Introducing
By revising the fourth edition of the WHO Classification of Central Nervous System Tumors1 in 2016, the classification of gliomas has undergone significant modifications. The Consortium to Advise Molecular and Functional Approaches to CNS Tumour Taxonomy, not officially WHO (cIMPACT-NOW)2,3,4, subsequently suggested further refinements of the classification. These documents allow glioblastoma to be diagnosed not only on the basis of histology, but also on the basis of many molecular markers and recommend that the term ‘IDH-mutant glioblastoma’ be discontinued. The European Association of Neuro-Oncology (EANO) found it appropriate to amend its recommendations for the care of adult patients with glioma5 to take account of these developments (Box 1). Prevention, early diagnosis and screening, integrated histomolecular diagnostics, therapy, and follow-up care of adult patients with diffuse gliomas are provided by the existing evidence-based recommendations. The scope of this guidance document goes beyond issues such as differential diagnosis, adverse effects of treatment, and supportive and palliative care.
Methodology
The task force nominated by the EANO Executive Board, following a recommendation by the Chair of the EANO Guidelines Committee, formulated these evidence-based guidelines. This task force comprises members of all fields involved in the diagnosis and treatment of glioma adults and represents EANO’s international character. References were collected from the PubMed database between January 2011 and July 2020 using the search terms’ glioma ‘,’ anaplastic ‘,’ astrocytoma’, ‘oligodendroglioma’, ‘glioblastoma’, ‘trial’, ‘clinical’, ‘surgery’, ‘radiotherapy’ and ‘chemotherapy’. Publications have also been found by searches of the libraries of the authors themselves. Only publications in English were reviewed. Under extraordinary circumstances, data accessible only in abstract form was included. On the basis of relevance to the wide scope of these guidelines, the definitive reference list was created. Recommendations for consensus have been reached by repeated dissemination of manuscript drafts and telephone conferences including Task Force representatives to address the most contentious areas. The key guidelines, with their evidence class (C) and level of recommendation (L)6, for the diagnosis and management of diffuse adult gliomas are listed at the end of each corresponding paragraph.
Epidemiology and prevention
The annual occurrence of gliomas worldwide is about six cases per 100,000 individuals. Men are 1.6-fold more likely than women to be diagnosed with gliomas. Although the overwhelming majority of cases are sporadic, gliomagenesis is associated with some hereditary tumour syndromes, including type I neurofibromatosis, tuberous sclerosis, Turcot syndrome, Li-Fraumeni syndrome and Lynch syndrome. At the initial diagnostic work-up, screening with neuroimaging is limited to patients with these syndromes8. Repeat neuroimaging is not recommended unless there are new neurological symptoms and indications that suggest an intracranial lesion, such as seizures, aphasia, hemiparesis or sensory deficits. Advice and screening of asymptomatic relatives of glioma patients that are found to be carriers of gliomagenesis-related germline mutations should be performed with caution and in consultation with clinical geneticists. There are no proven steps in place to prevent gliomas from forming.
Medical review and history
The creation of neurological symptoms and signs allows the prediction of glioma growth dynamics: tumors that cause symptoms just weeks before diagnosis typically grow quickly, while those that cause symptoms usually grow steadily for years before being diagnosed. The symptoms and signs recorded the year before diagnosis in most people are non-specific (for instance, exhaustion or headache)9,10,11. Family risk or unusual exogenous risk factors (such as exposure to radiation) associated with brain tumor development may be revealed in a discussion of the patient’s history. To obtain a reliable background, information from relatives might be needed. There is also a need to establish firm guidelines about when and how to include family members and caregivers and how to determine the medical decision-making ability of patients with brain tumours12.
New-onset epilepsy, focal deficits (such as paresis or sensory disturbances), neurocognitive dysfunction, and symptoms and signs of elevated intracranial pressure are distinctive types of clinical presentation. In order to distinguish primary brain tumours from brain metastases and contraindications for neurosurgical procedures, the physical examination of patients with brain tumours focuses on detecting systemic cancer. Any of the findings of the neurological test can be reported on the scale of the Neurological Assessment in Neuro-Oncology (NANO)13. Beyond recording performance status and undertaking a Mini Mental State Evaluation (MMSE)15 or a Montreal Cognitive Assessment (MoCA)16, neurocognitive assessment using a standardized test battery14 has become increasingly popular. Despite its drawbacks, MMSE is widely used for the diagnosis of the neurocognitive disorder as a screening tool and remains freely available for individual use.