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Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.

IMPORTANCE Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor.OBJECTIVE To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. MAIN OUTCOMES AND MEASURESProgression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group. RESULTSOf the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone. CONCLUSIONS AND RELEVANCEIn the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00916409

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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.

clinicaltrials.gov Identifier: NCT00916409.

Highlights d Flow cytometry, RNA-seq, and protein and image analyses reveal brain TME complexity d Glioma IDH mutation status and brain metastasis primary tumors shape the brain TME d Microglia and monocyte-derived macrophages exhibit multifaceted activation d TME immune cells show disease-and cell-type-specific expression patterns

Association for NeuroOncology (EANO) (2017). European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncology, 18(6):e315-e329. DOI: https://doi.org/10.1016/ S1470-2045(17) Implementing this guideline requires multidisciplinary and multiprofessional structures of care and defined processes of diagnosis and treatment.