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Patients with brain tumours are motivated to participate in clinical trials involving repeat tissue sampling. Normalising the use of neoadjuvant and staged surgical trials necessitates collaboration among patients, regulatory agencies, and researchers. Initial and repetitive tissue sampling plays a crucial role in enhancing our understanding of resistance mechanisms and vulnerabilities in brain tumour therapy. Standardising biopsy techniques and ensuring technical uniformity across institutions are vital for effective interinstitutional collaboration. Although liquid biopsy technologies hold promise, they are not yet ready to replace tissue analysis. Clear communication about the risks and benefits of biopsies is essential, particularly regarding potential postoperative deficits. Changes in mindset and neurosurgical culture are imperative to achieve much needed breakthroughs in the development of new, effective therapies for brain tumours., Competing Interests: Declaration of interests MG declares research grant support from Evgen Pharm. KCS declares honoraria from Springworks Therapeutics and Novartis; declares research funding to her institution from Springworks Therapeutics; and serves on a data and safety monitoring board for Advarra. TFC is cofounder, major stock holder, consultant, and board member of Katmai Pharmaceuticals; holds stock for Erasca; is a member of the board and paid consultant for the 501c3 Global Coalition for Adaptive Research; holds stock in Chimerix and receives milestone payments and possible future royalties; is a member of the scientific advisory board for Break Through Cancer foundation and Cure Brain Cancer Foundation; has provided paid consulting services to Symbio, Mundipharma, Tango BlueRock, Vida Ventures, Lista Therapeutics, Stemline, Novartis, Roche, Sonalasense, Sagimet, Clinical Care Options, Ideology Health, Servier, Jubilant, Immvira, Gan & Lee, BrainStorm, Katmai, Sapience, Inovio, Vigeo Therapeutics, DNATrix, Tyme, SDP, Kintara, Bayer, Merck, Boehringer Ingelheim, VBL, Amgen, Kiyatec, AbbVie, VBI, Deciphera, Agios, Novocure, and Medscape; and has contracts with UCLA for the Brain Tumour Programme with Roche, VBI, Merck, Novartis, and Bristol Myers Squibb. The Regents of the University of California, TFC's employer, has licensed intellectual property co-invented by TFC to Katmai Pharmaceuticals. GL is consultant advisor for Agenus, Amgen, Array Biopharma, AstraZeneca, Bayer, BioNTech, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics, IOBiotech, Immunocore, Innovent Biologics USA, Merck Sharpe & Dohme, Novartis, PHMR, Pierre Fabre, and Regeneron. AC declares research funding and honoraria from AstraZeneca, Benevolent AI, Duke Street Bio, and Evgen Pharmaceuticals; and has received honoraria from Storm Therapeutics. MSA declares a grant from Seagen; declares consulting fees from Bayer, Kiyatec, Insightec, GSK, Xoft, Nuvation, SDP Oncology, Apollomics, Prelude, Janssen, Voyager Therapeutics, Viewray, Caris Lifesciences, Pyramid Biosciences, Varian Medical Systems, Cairn Therapeutics, Anheart Therapeutics, Theraguix, Menarini Ricerche, Sumitomo Pharma Oncology, Autem Therapeutics, GT Medical Technologies, Allovir, and Equillium Bio; is on the data and safety monitoring board for VBI Vaccines; is on the scientific advisory board of Modifi biosciences and Bugworks; and is a shareholder for Mimivax, Cytodyn, MedInnovate Advisors, and Trisalus Lifesciences. SB reports consulting fees from and is a member of the advisory boards of Telix, Servier, Bayer, and Novocure; and research grants from Incyte, GSK, Lilly, Kite, and Novocure. JdG reports being an advisory board member for Kintara Pharmaceuticals, Kazia, MundiPharma, Insightec, Monteris, Carthera, Samus, Sapience, DSP Pharma, Telix, Servier, Alpha Pharmaceuticals, Nervianos, and CapitalOne; is a data safety monitoring board member for Chimerix and VBI; and has consulted for MundiPharma, Insightec, Carthera, Kintara, Deciphera, Kazia, and Nervianos. IP reports research funding from Merck. TCB reports consulting roles for Predicine; has received financial support from AbbVie and Predicine, with consulting fees paid to Mayo Clinic; and has been a member of the advisory board for Neurametrix. MPr reports honoraria from the following for-profit companies: Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman Group, CMC Contrast, GSK, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dohme, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Boehringer Ingelheim, Telix, and Medscape. JCT reports research grants from Novocure and Munich Surgical Imaging; being on the advisory board of Advanced Accelerator Applications, Novartis; and Servier; and has received royalties from Springer Publishing. MPl reports being a founder of Tcelltech; has received research support from Bayer, Roche, Pfizer, and Merck; and is an advisory board member of Bayer and Servier. SD is speaker for the Congress of Neurological Surgeons (CNS) and the American Association of Neurological Surgeons; receives research funding from Alkermes; is a member of the Subcortical Surgery Group advisory board; has received royalties from Oxford University Press; and is provincial lead for CNS Oncology at Ontario Health. KT reports consulting fees from Oncohereos Biosciences; and advisory board roles for Advanced Accelerator Applications, Novartis; Sage Therapeutics; FYR Diagnostics; Cordance Medical; Telo Therapeutics; and Modifi Bio. MAV reports clinical trial funding to their institution from DeNovo Pharma, Infuseon, and Oncosynergy; and received honoraria fees from Biodexa and Servier Pharma. MW reports research grants from Novartis, Quercis, and Versameb; honoraria for advisory boards from Roche and Servier; and honoraria for consultation from Bayer, Curevac, Medac, Neurosense, Novartis, Novocure, Orbus, Philogen, and Servier. JRW reports research funding from AnHeart Therapeutics to their institution; received consulting fees from AnHeart Therapeutics and Servier; being on advisory boards for Roche and Merck; is a data safety monitoring member for Telix Pharmaceuticals; and is an employee of The Walter and Eliza Hall Institute and could be eligible for milestone and royalty payments related to Venetoclax. MK reports research grants from Bristol Myers Squibb, AbbVie, BioNTech, CNS Pharmaceuticals, Daiichi Sankyo, Immorna Therapeutics, Immvira Therapeutics, and Personalis; received consulting fees from The Jackson Lab for Genomic Research, AnHeart Therapeutics, Berg Pharma, George Clinical, Manarini Stemline, and Servier; received honoraria from GSK; and is on a data safety monitoring board for BPGbio. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Theranostics integrate molecular imaging and targeted radionuclide therapy for personalised cancer therapy. Theranostic treatments have shown meaningful efficacy in randomised clinical trials and are approved for clinical use in prostate cancer and neuroendocrine tumours. Brain tumours represent an unmet clinical need and theranostics might offer effective treatment options, although specific issues need to be considered for clinical development. In this Policy Review, we discuss opportunities and challenges of developing targeted radionuclide therapies for the treatment of brain tumours including glioma, meningioma, and brain metastasis. The rational choice of molecular treatment targets is highlighted, including the potential relevance of different types of targeted radionuclide therapeutics, and the role of the blood-brain barrier and blood-tumour barrier. Furthermore, we discuss considerations for effective clinical trial design and conduct, as well as logistical and regulatory challenges for implementation of radionuclide therapies into neuro-oncological practice. Rational development will foster successful translation of the theranostic concept to brain tumours., Competing Interests: Declaration of interests NLA has received honoraria for consultation or advisory board participation from Novartis, Advanced Accelerator Applications, Servier, and Telix Pharmaceuticals; and has received research funding from Novocure. ELR has received a research grant from Bristol Myers Squibb; and received honoraria for advisory board participation from AstraZeneca, Bayer, Janssen, Leo Pharma, Pfizer, Pierre Fabre, Roche, Seagen, and Servier. GM has received honoraria for speaker activity and travel support from Brainlab and Accuray. MJM has received research funding from Bristol Myers Squibb and travel support from Pierre Fabre. NG received honoraria for lectures from Blue Earth Diagnostics and for advisory board participation from Telix Pharmaceuticals. MN has received speaker fees for educational lectures from AstraZeneca and Brainlab. MS has received consultancy fees from Bracco and speaker fees from AuntMinnie and Fondazione Internazionale Menarini (all paid to institution). AV has received honoraria for consultation or advisory board participation from Curium, Eisai, General Electrics, and Novartis. MW has received research grants from Quercis and Versameb; and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Neurosense, Novartis, Novocure, Orbus, Philogen, Roche, and Servier. MP has received honoraria for lectures, consultation, or advisory board participation from Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman Group, CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Eli Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Böhringer-Ingelheim, Telix, and Medscape. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Response Assessment in Neuro-Oncology (RANO) response criteria have been established and were updated in 2023 for MRI-based response evaluation of diffuse gliomas in clinical trials. In addition, PET-based imaging with amino acid tracers is increasingly considered for disease monitoring in both clinical practice and clinical trials. So far, a standardised framework defining timepoints for baseline and follow-up investigations and response evaluation criteria for PET imaging of diffuse gliomas has not been established. Therefore, in this Policy Review, we propose a set of criteria for response assessment based on amino acid PET imaging in clinical trials enrolling participants with diffuse gliomas as defined in the 2021 WHO classification of tumours of the central nervous system. These proposed PET RANO criteria provide a conceptual framework that facilitates the structured implementation of PET imaging into clinical research and, ultimately, clinical routine. To this end, the PET RANO 1.0 criteria are intended to encourage specific investigations of amino acid PET imaging of gliomas., Competing Interests: Declaration of interests NLA has received honoraria for consultation or advisory board participation from Novartis (Advanced Accelerator Applications), Telix Pharmaceuticals, and Servier; and research funding from Novocure. NG received honoraria for lectures from Blue Earth Diagnostics and honoraria for advisory board participation from Telix Pharmaceuticals. BME is on the advisory board and is a paid consultant for Medicenna, MedQIA, Servier Pharmaceuticals, Siemens, Janssen Pharmaceuticals, Imaging Endpoints, Kazia, Chimerix, Sumitomo Dainippon Pharma Oncology, ImmunoGenesis, Ellipses Pharma, Monteris, Neosoma, Alpheus Medical, Sagimet Biosciences, Sapience Therapeutics, Orbus Therapeutics, and the Global Coalition for Adaptive Research. MJvdB has received honoraria from Roche, AstraZeneca, Servier, Boehringer, Genenta, Fore Biotherapeutics, Incyte, and Nerviano. ELR reports personal financial interests as an advisory board member for Bayer, Janssen, Leo Pharma, Pierre Fabre, Roche, Seattle Genetics, and Servier; and institutional funding from Bristol Myers Squibb. MJM has received research support from Bristol Myers Squibb and travel support from Pierre Fabre. GM has received honoraria for lectures from BrainLab. RR has received research grants from Bayer, and honoraria for lectures or consulting from UCB, Novocure, Genenta, Curevac, and Servier. AMS has received research support to his institution from Medimmune, AVID, Telix Pharmaceuticals, ITM, Fusion, Cyclotek, Adalta, TheraMyc, Curis, Humanigen, and Antengene; funding support from the Medical Research Future Fund, Australian Brain Cancer Mission, Cure Brain Cancer Foundation, National Breast Cancer Foundation, Australian Cancer Research Foundation, National Imaging Facility, and Victorian Cancer Agency; and is a National Health and Medical Research Council Investigator. MS has received honoraria for consultancy from Bracco and honoraria for lectures from GE Healthcare, AuntMinnie, and Fondazione Internazionale Menarini (all paid to their institution). BS has received honoraria for lectures and consultation from Novocure. J-CT has received honoraria for lectures, consultation, or advisory board participation from SeagGen, AAA-Novartis, Novocure, and Munich Surgical Imaging. AV has received honoraria for lectures and advisory board participation from Curium, Eisai, and General Electrics. MW has received research grants from Quercis and Versameb; and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Novartis, Novocure, Orbus, Philogen, Roche, and Servier. PYW has received research support from AstraZeneca, Black Diamond, Bristol Myers Squibb, Celgene, Chimerix, Eli Lilly, Erasca, Genentech/Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Servier, Vascular Biogenics, and VBI Vaccines; and honoraria for serving as a consultant or on advisory boards for AstraZeneca, Black Diamond, Celularity, Chimerix, Day One Bio, Genenta, GSK, Merck, Mundipharma, Novartis, Novocure, Nuvation Bio, Prelude Therapeutics, Sapience, Servier, Sagimet, Vascular Biogenics, and VBI Vaccines. MP has received honoraria for lectures, consultation, or advisory board participation from Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman Group, CMC Contrast, GSK, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dohme, Tocagen, Adastra, Gan & Lee Pharmaceuticals, and Servier; and travel support from Servier, Roche, and Medsir., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The European Association of Neuro-Oncology (EANO) and EUropean RAre CANcer (EURACAN) guideline provides recommendations for the diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma. The guideline is based on the 2016 WHO classification of tumours of the CNS and on scientific developments published since 1980. It aims to provide direction for diagnostic and management decisions, and for limiting unnecessary treatments and cost. In view of the scarcity of data in adults with medulloblastoma, we base our recommendations on adult data when possible, but also include recommendations derived from paediatric data if justified. Our recommendations are a resource for professionals involved in the management of post-pubertal and adult patients with medulloblastoma, for patients and caregivers, and for health-care providers in Europe. The implementation of this guideline requires multidisciplinary structures of care, and defined processes of diagnosis and treatment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The European Association for Neuro-Oncology guideline provides recommendations for the clinical care of adult patients with astrocytic and oligodendroglial gliomas, including glioblastomas. The guideline is based on the 2016 WHO classification of tumours of the central nervous system and on scientific developments since the 2014 guideline. The recommendations focus on pathological and radiological diagnostics, and the main treatment modalities of surgery, radiotherapy, and pharmacotherapy. In this guideline we have also integrated the results from contemporary clinical trials that have changed clinical practice. The guideline aims to provide guidance for diagnostic and management decisions, while limiting unnecessary treatments and costs. The recommendations are a resource for professionals involved in the management of patients with glioma, for patients and caregivers, and for health-care providers in Europe. The implementation of this guideline requires multidisciplinary structures of care, and defined processes of diagnosis and treatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The WHO classification of brain tumours describes 15 subtypes of meningioma. Nine of these subtypes are allotted to WHO grade I, and three each to grade II and grade III. Grading is based solely on histology, with an absence of molecular markers. Although the existing classification and grading approach is of prognostic value, it harbours shortcomings such as ill-defined parameters for subtypes and grading criteria prone to arbitrary judgment. In this study, we aimed for a comprehensive characterisation of the entire molecular genetic landscape of meningioma to identify biologically and clinically relevant subgroups., Methods: In this multicentre, retrospective analysis, we investigated genome-wide DNA methylation patterns of meningiomas from ten European academic neuro-oncology centres to identify distinct methylation classes of meningiomas. The methylation classes were further characterised by DNA copy number analysis, mutational profiling, and RNA sequencing. Methylation classes were analysed for progression-free survival outcomes by the Kaplan-Meier method. The DNA methylation-based and WHO classification schema were compared using the Brier prediction score, analysed in an independent cohort with WHO grading, progression-free survival, and disease-specific survival data available, collected at the Medical University Vienna (Vienna, Austria), assessing methylation patterns with an alternative methylation chip., Findings: We retrospectively collected 497 meningiomas along with 309 samples of other extra-axial skull tumours that might histologically mimic meningioma variants. Unsupervised clustering of DNA methylation data clearly segregated all meningiomas from other skull tumours. We generated genome-wide DNA methylation profiles from all 497 meningioma samples. DNA methylation profiling distinguished six distinct clinically relevant methylation classes associated with typical mutational, cytogenetic, and gene expression patterns. Compared with WHO grading, classification by individual and combined methylation classes more accurately identifies patients at high risk of disease progression in tumours with WHO grade I histology, and patients at lower risk of recurrence among WHO grade II tumours (p=0·0096) from the Brier prediction test). We validated this finding in our independent cohort of 140 patients with meningioma., Interpretation: DNA methylation-based meningioma classification captures clinically more homogenous groups and has a higher power for predicting tumour recurrence and prognosis than the WHO classification. The approach presented here is potentially very useful for stratifying meningioma patients to observation-only or adjuvant treatment groups. We consider methylation-based tumour classification highly relevant for the future diagnosis and treatment of meningioma., Funding: German Cancer Aid, Else Kröner-Fresenius Foundation, and DKFZ/Heidelberg Institute of Personalized Oncology/Precision Oncology Program., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The management of primary CNS lymphoma is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the very few controlled studies available. In 2013, the European Association of Neuro-Oncology created a multidisciplinary task force to establish evidence-based guidelines for immunocompetent adults with primary CNS lymphoma. In this Review, we present these guidelines, which provide consensus considerations and recommendations for diagnosis, assessment, staging, and treatment of primary CNS lymphoma. Specifically, we address aspects of care related to surgery, systemic and intrathecal chemotherapy, intensive chemotherapy with autologous stem-cell transplantation, radiotherapy, intraocular manifestations, and management of elderly patients. The guidelines should aid clinicians in their daily practice and decision making, and serve as a basis for future investigations in neuro-oncology., (Copyright © 2015 Elsevier Ltd. All rights reserved.)