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(1) Background: Clinical aspects like sex, age, Karnofsky Performance Scale (KPS) and psychosocial distress can affect the health-related quality of life (HR-QoL) and treatment satisfaction of patients with malignant isocitrate dehydrogenase wild-type (IDHwt) gliomas and caregivers. (2) Methods: We prospectively investigated the HR-QoL and patient/caregiver treatment satisfaction in a cross-sectional study with univariable and multiple regression analyses. Questionnaires were applied to investigate the HR-QoL (EORTC QLQ-C30, QLQ-BN20) and treatment satisfaction (EORTC PATSAT-C33). (3) Results: A cohort of 61 patients was investigated. A higher KPS was significantly associated with a better HR-QoL regarding the functional scales of the EORTC QLQ-C30 ( p < 0.004) and a lower symptom burden regarding the EORTC QLQ-BN20 ( p < 0.001). The patient treatment satisfaction was significantly poorer in the patients older than 60 years in the domain of family involvement ( p = 0.010). None of the investigated aspects showed a significant impact on the treatment satisfaction of caregivers. (4) Conclusions: We demonstrated that in patients with IDHwt gliomas, the KPS was the most important predictor for a better HR-QoL in functional domains. Data on the HR-QoL and treatment satisfaction in patients with IDHwt gliomas and their caregivers are rare; therefore, further efforts should be made to improve supportive care in this highly distressed cohort.

Cerebral metastases in patients with metastatic lung cancer are found in more than 30% of patients at baseline and manifest themselves in two out of three patients during disease evolution. For a long time, the cerebral manifestation of the disease was classified as prognostically unfavorable and hence such patients were regularly excluded from therapy studies. In the context of targeted molecular therapy strategies and established immuno-oncological systemic therapies, the blood-brain barrier no longer represents an insurmountable barrier. However, the treatment of brain metastases requires decision making in a multidisciplinary team within dedicated lung cancer and/or oncology centers. The differentiated treatment decision is based on the number, size and location of the brain metastases, neurology and general condition, comorbidities, potential life expectancy and the patient's wishes, but also tumor biology including molecular targets, extra-cranial tumor burden and availability of a CNS-effective therapy. Systemic therapies as well as neurosurgical and radiotherapeutic concepts are now often combined for optimized and prognosis-improving therapeutic strategies., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objective: Maximal resection of brain metastases (BMs) improves both progression-free survival and overall survival (OS). Fluorescein sodium (FL) in combination with the YELLOW 560-nm filter is a safe and feasible method for visualizing residual tumor tissue during BM resection. The authors of this study aimed to show that use of FL would positively influence the volumetric extent of resection (EOR) and thus the survival outcome in patients undergoing BM resection., Methods: Analyzing their institution's prospective brain tumor registry, the authors identified 539 consecutive patients with BMs (247 women, mean age 62.8 years) by using preoperative high-quality MR images for volumetric analysis. BMs were resected under white light (WL) in 293 patients (54.4%; WL group) and under FL guidance in 246 patients (45.6%; FL group). Sex, age, presurgical Karnofsky Performance Status (KPS), recursive partitioning analysis class, and adjuvant treatment modalities were well balanced between the two groups. Volumetric analysis was performed in a blinded fashion by quantifying pre- and postoperative tumor volume based on gadolinium-enhanced T1-weighted sequences., Results: In the FL group, the postoperative tumor volume was significantly smaller (p = 0.01), and hence the quantitative EOR was significantly larger (p = 0.024) and OS was significantly longer (p = 0.0001) (log-rank testing). Multivariate Cox regression modeling showed that age, presurgical KPS, metastasis status, and FL-guided resection are independent prognostic factors for survival., Conclusions: Compared with WL resection, FL-guided BM resection increased resection quality, significantly improved EOR, and prolonged OS.

Background: The expression level of the programmed cell death ligand 1 (PD-L1) appears to be a predictor for response to immunotherapy using checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC). As differences in terms of PD-L1 expression levels in the extracranial primary tumor and the brain metastases may occur, a reliable method for the non-invasive assessment of the intracranial PD-L1 expression is, therefore of clinical value. Here, we evaluated the potential of radiomics for a non-invasive prediction of PD-L1 expression in patients with brain metastases secondary to NSCLC., Patients and Methods: Fifty-three NSCLC patients with brain metastases from two academic neuro-oncological centers (group 1, n = 36 patients; group 2, n = 17 patients) underwent tumor resection with a subsequent immunohistochemical evaluation of the PD-L1 expression. Brain metastases were manually segmented on preoperative T1-weighted contrast-enhanced MRI. Group 1 was used for model training and validation, group 2 for model testing. After image pre-processing and radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. The radiomics model was trained and validated using random stratified cross-validation. Finally, the best-performing radiomics model was applied to the test data. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analyses., Results: An intracranial PD-L1 expression (i.e., staining of at least 1% or more of tumor cells) was present in 18 of 36 patients (50%) in group 1, and 7 of 17 patients (41%) in group 2. Univariate analysis identified the contrast-enhancing tumor volume as a significant predictor for PD-L1 expression (area under the ROC curve (AUC), 0.77). A random forest classifier using a four-parameter radiomics signature, including tumor volume, yielded an AUC of 0.83 ± 0.18 in the training data (group 1), and an AUC of 0.84 in the external test data (group 2)., Conclusion: The developed radiomics classifiers allows for a non-invasive assessment of the intracranial PD-L1 expression in patients with brain metastases secondary to NSCLC with high accuracy., (© 2023. The Author(s).)

Purpose: This study aimed to verify the feasibility, safety, and benefit of using fluorescein sodium (FL) and a YELLOW 560 nm filter in posterior fossa tumors in children., Methods: All cases of pediatric posterior fossa tumors that have undergone surgery using fluorescein (2018-2022) have been included and were examined retrospectively. In those cases where resection of the tumor was planned, a blinded neuroradiologist distinguished gross total resection and subtotal resection according to the postoperative MRI findings. The surgical report and medical files were reviewed regarding the intraoperative staining grade and adverse events. The grade of fluorescent staining of the targeted lesion was assessed as described in the surgical reports. The screening was conducted for any reference to the degree of fluorescent staining: "intense," "medium," "slight," and "no staining.", Results: 19 cases have been included. In 14 cases, a complete resection was initially intended. In 11 of these cases, a gross total resection could be achieved (78.6%). Staining was described as intense in most cases (58.8%). Except for yellow-colored urine, no side effects obviously related to FL were found throughout the observation period., Conclusion: In combination with a specific filter, FL is a reliable, safe, and feasible tool in posterior fossa surgery in children., (© 2022. The Author(s).)

Brain-tumor-initiating cells (BTICs) of proneural and mesenchymal origin contribute to the highly malignant phenotype of glioblastoma (GB) and resistance to current therapies. BTICs of different subtypes were challenged with oxidative phosphorylation (OXPHOS) inhibition with metformin to assess the differential effects of metabolic intervention on key resistance features. Whereas mesenchymal BTICs varied according to their invasiveness, they were in general more glycolytic and less responsive to metformin. Proneural BTICs were less invasive, catabolized glucose more via the pentose phosphate pathway, and responded better to metformin. Targeting glycolysis may be a promising approach to inhibit tumor cells of mesenchymal origin, whereas proneural cells are more responsive to OXPHOS inhibition. Future clinical trials exploring metabolic interventions should account for metabolic heterogeneity of brain tumors.

Background: The BRAF V600E mutation is present in approximately 50% of patients with melanoma brain metastases and an important prerequisite for response to targeted therapies, particularly BRAF inhibitors. As heterogeneity in terms of BRAF mutation status may occur in melanoma patients, a wild-type extracranial primary tumor does not necessarily rule out a targetable mutation in brain metastases using BRAF inhibitors. We evaluated the potential of MRI radiomics for a noninvasive prediction of the intracranial BRAF mutation status., Methods: Fifty-nine patients with melanoma brain metastases from two university brain tumor centers (group 1, 45 patients; group 2, 14 patients) underwent tumor resection with subsequent genetic analysis of the intracranial BRAF mutation status. Preoperative contrast-enhanced MRI was manually segmented and analyzed. Group 1 was used for model training and validation, group 2 for model testing. After radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. Finally, the best performing radiomics model was applied to the test data. Diagnostic performances were evaluated using receiver operating characteristic (ROC) analyses., Results: Twenty-two of 45 patients (49%) in group 1, and 8 of 14 patients (57%) in group 2 had an intracranial BRAF V600E mutation. A linear support vector machine classifier using a six-parameter radiomics signature yielded an area under the ROC curve of 0.92 (sensitivity, 83%; specificity, 88%) in the test data., Conclusions: The developed radiomics classifier allows a noninvasive prediction of the intracranial BRAF V600E mutation status in patients with melanoma brain metastases with high diagnostic performance., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Confocal laser endomicroscopy (CLE) is an established tool in basic research for tissue imaging at the level of microstructures. Miniaturization and refinement of the technology have made this modality available for operative imaging with a handheld device. Sufficient image contrast is provided by the preoperative application of fluorescein sodium. The authors report their first experiences in a clinical case series using the new confocal laser endomicroscope., Methods: Handling, operative workflow, and visualization of the CLE were critically evaluated in 12 cases of different CNS tumors. Three different imaging positions in relation to the tumor were chosen: the tumor border (I), tumor center (II), and perilesional zone (III). Respective diagnostic sampling with H & E staining and matching intraoperative neuronavigation and microscope images are provided., Results: CLE was found to be beneficial in terms of high-quality visualization of fine structures and for displaying hidden anatomical details. The handling of the device was good, and the workflow was easy., Conclusions: Handling ergonomics and image acquisition are intuitive. The endomicroscope allows excellent additional visualization of microstructures in the surgical field with a minimally invasive technique and could improve safety and clinical outcomes. The new confocal laser endomicroscope is an advanced tool with the potential to change intracranial tumor surgery. Imaging of these microstructures is novel, and research with comparative validation with traditional neuropathological assessments is needed.

Background: Brain metastases (BM) frequently cause focal neurological deficits leading to a reduced Karnofsky performance score (KPS). Since KPS is routinely used to guide the choice of adjuvant therapy, we hypothesized that improving KPS by surgical resection may improve the chance for adjuvant treatment and ultimately result in better survival. We therefore analyzed the course of a large cohort undergoing resection of symptomatic brain metastases in the context of further treatment and clinical outcome., Patients and Methods: In a bi-centric retrospective analysis we retrieved baseline, clinical, and treatment-related parameters of patients operated on BM between 2010 and 2019. Survival was calculated using Kaplan-Meier estimates; prognostic factors for survival were analyzed by Log-rank test and Cox proportional hazards., Results: We included 750 patients with a median age of 61 (19-87) years. The functional status was significantly improved by surgical resection, with a median preoperative (KPS) of 80 (10-100) increasing to 90 (0-100) after surgery (P < .0001). Moreover, surgery improved the RTOG recursive partitioning analysis (RPA) class from III to I/II in 82 patients. Postoperative local radiotherapy and systemic treatment were associated with significantly longer survival (P < .0001 for each). Systemic treatment was provided significantly more frequently in patients with a fair postoperative clinical status (KPS ≥ 70; P < .0001). The postoperative clinical status, postoperative radiotherapy, systemic treatment, controlled systemic disease and < 4 BM were independent predictors for survival., Conclusion: The resection of symptomatic BM may restore clinical status, so enhancing the likelihood of receiving adjuvant treatment, and therefore leading to improved overall survival., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Mesenchymal stem cells (MSCs) show an inherent brain tumor tropism that can be exploited for targeted delivery of therapeutic genes to invasive glioma. We assessed whether a motile MSC-based local immunomodulation is able to overcome the immunosuppressive glioblastoma microenvironment and to induce an antitumor immune response., Experimental Design: We genetically modified MSCs to coexpress high levels of IL12 and IL7 (MSC IL7/12 , Apceth-301). Therapeutic efficacy was assessed in two immunocompetent orthotopic C57BL/6 glioma models using GL261 and CT2A. Immunomodulatory effects were assessed by multicolor flow cytometry to profile immune activation and exhaustion of tumor-infiltrating immune cells. Diversity of the tumor-specific immune response as analyzed using T-cell receptor sequencing., Results: Intratumoral administration of MSC IL7/12 induced significant tumor growth inhibition and remission of established intracranial tumors, as demonstrated by MR imaging. Notably, up to 50% of treated mice survived long-term. Rechallenging of survivors confirmed long-lasting tumor immunity. Local treatment with MSC IL7/12 was well tolerated and led to a significant inversion of the CD4 + /CD8 + T-cell ratio with an intricate, predominantly CD8 + effector T-cell-mediated antitumor response. T-cell receptor sequencing demonstrated an increased diversity of TILs in MSC IL7/12 -treated mice, indicating a broader tumor-specific immune response with subsequent oligoclonal specification during generation of long-term immunity., Conclusions: Local MSC-based immunomodulation is able to efficiently alter the immunosuppressive microenvironment in glioblastoma. The long-lasting therapeutic effects warrant a rapid clinical translation of this concept and have led to planning of a phase I/II study of apceth-301 in recurrent glioblastoma., (©2020 American Association for Cancer Research.)

OBJECTIVE Warning criteria for monitoring of motor evoked potentials (MEP) after direct cortical stimulation during surgery for supratentorial tumors have been well described. However, little is known about the value of MEP after transcranial electrical stimulation (TES) in predicting postoperative motor deficit when monitoring threshold level. The authors aimed to evaluate the feasibility and value of this method in glioma surgery by using a new approach for interpreting changes in threshold level involving contra- and ipsilateral MEP. METHODS Between November 2013 and December 2014, 93 patients underwent TES-MEP monitoring during resection of gliomas located close to central motor pathways but not involving the primary motor cortex. The MEP were elicited by transcranial repetitive anodal train stimulation. Bilateral MEP were continuously evaluated to assess percentage increase of threshold level (minimum voltage needed to evoke a stable motor response from each of the muscles being monitored) from the baseline set before dural opening. An increase in threshold level on the contralateral side (facial, arm, or leg muscles contralateral to the affected hemisphere) of more than 20% beyond the percentage increase on the ipsilateral side (facial, arm, or leg muscles ipsilateral to the affected hemisphere) was considered a significant alteration. Recorded alterations were subsequently correlated with postoperative neurological deterioration and MRI findings. RESULTS TES-MEP could be elicited in all patients, including those with recurrent glioma (31 patients) and preoperative paresis (20 patients). Five of 73 patients without preoperative paresis showed a significant increase in threshold level, and all of them developed new paresis postoperatively (transient in 4 patients and permanent in 1 patient). Eight of 20 patients with preoperative paresis showed a significant increase in threshold level, and all of them developed postoperative neurological deterioration (transient in 4 patients and permanent in 4 patients). In 80 patients no significant change in threshold level was detected, and none of them showed postoperative neurological deterioration. The specificity and sensitivity in this series were estimated at 100%. Postoperative MRI revealed gross-total tumor resection in 56 of 82 patients (68%) in whom complete tumor resection was attainable; territorial ischemia was detected in 4 patients. CONCLUSIONS The novel threshold criterion has made TES-MEP a useful method for predicting postoperative motor deficit in patients who undergo glioma surgery, and has been feasible in patients with preoperative paresis as well as in patients with recurrent glioma. Including contra- and ipsilateral changes in threshold level has led to a high sensitivity and specificity.

Stem cell-based therapies for neurological disorders, including brain tumors, advance continuously toward clinical trials. Optimized cell delivery to the central nervous system remains a challenge since direct intracerebral injection is an invasive method with low transplantation efficiency. We investigated the feasibility of intranasal administration of neural stem/progenitor cells (NSPCs) as an alternative, noninvasive, and direct passage for the delivery of stem cells to target malignant gliomas. Tumor-targeting and migratory pathways of murine and human NSPCs were investigated by intravital magnetic resonance imaging and in histological time course analyses in the intracerebral U87, NCE-G55T2, and syngenic Gl261 glioblastoma models. Intranasally administered NSPCs displayed a rapid, targeted tumor tropism with significant numbers of NSPCs accumulating specifically at the intracerebral glioma site within 6 hours after intranasal delivery. Histological time series analysis revealed that NSPCs migrated within the first 24 hours mainly via olfactory pathways but also by systemic distribution via the microvasculature of the nasal mucosa. Intranasal application of NSPCs leads to a rapid, targeted migration of cells toward intracerebral gliomas. The directional distribution of cells accumulating intra- and peritumorally makes the intranasal delivery of NSPCs a promising noninvasive and convenient alternative delivery method for the treatment of malignant gliomas with the possibility of multiple dosing regimens.

Neural stem/progenitor cells (NSPCs) display inherent pathotropic properties that can be exploited for targeted delivery of therapeutic genes to invasive malignancies in the central nervous system. Optimizing transplantation efficiency will be essential for developing relevant NSPC-based brain tumor therapies. To date, the real-world issue of handling and affixing NSPCs in the context of the neurosurgical resection cavity has not been addressed. Stem cell transplantation using biocompatible devices is a promising approach to counteract poor NSPC graft survival and integration in various types of neurological disorders. Here, we report the development of a 3-dimensional substrate that is based on extracellular matrix purified from tissue-engineered skin cultures (3DECM). 3DECM enables the expansion of embedded NSPCs in vitro while retaining their uncommitted differentiation status. When implanted in intracerebral glioma models, NSPCs were able to migrate out of the 3DECM to targeted glioma growing in the contralateral hemisphere, and this was more efficient than the delivery of NSPC by intracerebral injection of cell suspensions. Direct application of a 3DECM implant into a tumor resection cavity led to a marked NSPC infiltration of recurrent glioma. The semisolid consistency of the 3DECM implants allowed simple handling during the surgical procedure of intracerebral and intracavitary application and ensured continuous contact with the surrounding brain parenchyma. Here, we demonstrate proof-of-concept of a matrix-supported transplantation of tumor-targeting NSPC. The semisolid 3DECM as a delivery system for NSPC has the potential to increase transplantation efficiency by reducing metabolic stress and providing mechanical support, especially when administered to the surgical resection cavity after brain tumor removal.

A major obstacle in the treatment of gliomas is the invasive capacity of the tumor cells. Previous studies have demonstrated the capability of neural stem cells (NSCs) to target these disseminated tumor cells and to serve as therapeutic delivery vehicles. Less is known about the factors involved in brain tumor tropism of NSCs and their interactions within the tumor environment. As gliomas progress and invade, an extensive modulation of the extracellular matrix (ECM) occurs. Tumor-ECM derived from six glioblastoma cell lines, ECM produced by normal human astrocytes and purified ECM compounds known to be upregulated in the glioma environment were analyzed for their effects on NSCs motility in vitro. We found that tumor-produced ECM was highly permissive for NSC migration. Laminin was the most permissive substrate for human NSC migration, and tenascin-C the strongest inducer of a directed human NSC migration (haptotaxis). A positive correlation between the degree of adhesion and migration of NSCs on different ECM compounds exists, as for glioma cells. Our in vitro data suggest that the ECM of malignant gliomas is a modulator of NSC migration. ECM proteins preferentially expressed in areas of glioma cell invasion may provide a permissive environment for NSC tropism to disseminated tumor cells.

Brain metastases are an increasingly frequent and serious clinical problem for cancer patients, especially those with advanced melanoma. Given the extensive tropism of neural stem/progenitor cells (NSPCs) for pathological areas in the central nervous system, we expanded investigations to determine whether NSPCs could also target multiple sites of brain metastases in a syngeneic experimental melanoma model. Using cytosine deaminase-expressing NSPCs (CD-NSPCs) and systemic 5-fluorocytosine (5-FC) pro-drug administration, we explored their potential as a cell-based targeted drug delivery system to disseminated brain metastases. Our results indicate a strong tropism of NSPCs for intracerebral melanoma metastases. Furthermore, in our therapeutic paradigm, animals with established melanoma brain metastasis received intracranial implantation of CD-NSPCs followed by systemic 5-FC treatment, resulting in a significant (71%) reduction in tumor burden. These data provide proof of principle for the use of NSPCs for targeted delivery of therapeutic gene products to melanoma brain metastases.

The transplantation of neural stem cells (NSCs) offers a new potential therapeutic approach as a cell-based delivery system for gene therapy in brain tumors. This is based on the unique capacity of NSCs to migrate throughout the brain and to target invading tumor cells. However, the signals controlling the targeted migration of transplanted NSCs are poorly defined. We analyzed the in vitro and in vivo effects of angiogenic growth factors and protein extracts from surgical specimens of brain tumor patients on NSC migration. Here, we demonstrate that vascular endothelial growth factor (VEGF) is able to induce a long-range attraction of transplanted human NSCs from distant sites in the adult brain. Our results indicate that tumor-upregulated VEGF and angiogenic-activated microvasculature are relevant guidance signals for NSC tropism toward brain tumors.

Assessment of therapy efficacy using animal models of tumorigenic cancer requires the ability to accurately measure changes in tumor volume over the duration of disease course. In order to be meaningful, in vivo tumor volume measurements by non-invasive techniques must correlate with tumor volume measurements from endpoint histological analysis. Tumor volume is frequently assessed by endpoint histological analyses approximating the tumor volume with geometric primitives such as spheroids and ellipsoids. In this study we investigated alternative techniques for quantifying histological volume measurements of tumors in a xenograft orthotopic mouse model of human glioblastoma multiforme, and compared these to in vivo tumor volume measurements based on magnetic resonance imaging (MRI) data. Two techniques leveraging three-dimensional (3D) image analysis methods were investigated. The first technique involves the reconstruction of a smoothed polygonal model representing the tumor volume from histological section images and is intended for accuracy and qualitative assessment of tumor burden by visualization, while a second technique which approximates the tumor volume as a series of slabs is presented as an abbreviated process intended to produce quantitatively similar volume measurements with a minimum of effort required on behalf of the investigator. New software (QuickVol) designed for use in the first technique, is also discussed. In cases where tumor growth is asymmetric and invasive, we found that 3D analysis techniques using histological section images produced volume measurements more consistent with in vivo volume measurements based on MRI data, than approximation of tumor volume using geometric primitives. Visualizations of the volumes represented by each of these techniques qualitatively support this finding, and suggest that future research using mouse models of glioblastoma multiforme (genetically engineered or xenograft) will benefit from the use of these or similar alternative tumor volume measurement techniques.

Targeting active angiogenesis, which is a major hallmark of malignant gliomas, is a potential therapeutic approach. For effective inhibition of tumor-induced neovascularization, antiangiogenic compounds have to be delivered in sufficient quantities over a sustained period of time. The short biological half-life of many antiangiogenic inhibitors and the impaired intratumoral blood flow create logistical difficulties that make it necessary to optimize drug delivery for the treatment of malignant gliomas. In this study, we compared the effects of endostatin delivered by daily systemic administration or local intracerebral microinfusion on established intracranial U87 human glioblastoma xenografts in nude mice. Noninvasive magnetic resonance imaging methods were used to assess treatment effects and additional histopathological analysis of tumor volume, microvessel density, proliferation, and apoptosis rate were performed. Three weeks of local intracerebral microinfusion of endostatin (2 mg/kg/day) led to 74% (P < 0.05) reduction of tumor volumes with decreased microvessel densities (33.5%, P < 0.005) and a 3-fold increased tumor cell apoptosis (P < 0.002). Systemic administration of a 10-fold higher amount of endostatin (20 mg/kg/day) did not result in a reduction of tumor volume nor in an increase of tumor cell apoptosis despite a significant decrease of microvessel densities (26.9%, P < 0.005). Magnetic resonance imaging was used to successfully demonstrate treatment effects. The local microinfusion of human endostatin significantly increased survival when administered at 2 mg/kg/day and was prolonged further when the dose was increased to 12 mg/kg/day. Our results indicate that the local intracerebral microinfusion of antiangiogenic compounds is an effective way to overcome the logistical problems of inhibiting glioma-induced angiogenesis.

Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, how to define those regions on the basis of preoperative imaging, and the optimal sample volume. Practical recommendations for tissue sampling are given for people with low-grade and high-grade gliomas, as well as for people with newly diagnosed and recurrent disease. Sampling of liquid biopsies is also addressed. A standardised workflow for subsequent handling of the resected tissue is proposed to avoid information loss due to decreasing tissue quality or insufficient clinical information. The recommendations offer a framework for prospective biobanking studies.