Surgeon experience in glioblastoma surgery of the elderly : a multicenter, retrospective cohort study

Purpose To assess the impact of individual surgeon experience on overall survival (OS), extent of resection (EOR) and surgery-related morbidity in elderly patients with glioblastoma (GBM), we performed a retrospective case-by-case analysis. Methods GBM patients aged≥65 years who underwent tumor resection at two academic centers were analyzed. The experience of each neurosurgeon was quantifed in three ways: (1) total number of previously performed glioma surgeries (lifetime experience); (2) number of surgeries performed in the previous fve years (medium-term experience) and (3) in the last two years (short-term experience). Surgeon experience data was correlated with survival (OS) and surrogate parameters for surgical quality (EOR, morbidity). Results 198 GBM patients (median age 73.0 years, median preoperative KPS 80, IDH-wildtype status 96.5%) were included. Median OS was 10.0 months (95% CI 8.0–12.0); median EOR was 89.4%. Surgery-related morbidity afected 19.7% patients. No correlations of lifetime surgeon experience with OS (P=.693), EOR (P=.693), and surgery-related morbidity (P=.435) were identifed. Adjuvant therapy was associated with improved OS (PConclusion Less experienced neurosurgeons achieve similar surgical results and outcome in elderly GBM patients within the setting of academic teaching hospitals. Adjuvant treatment and avoidance of surgery-related morbidity are crucial forgenerating a treatment beneft for this cohort.Peer reviewe

Deep learning-assisted radiomics facilitates multimodal prognostication for personalized treatment strategies in low-grade glioma

Determining the optimal course of treatment for low grade glioma (LGG) patients is challenging and frequently reliant on subjective judgment and limited scientific evidence. Our objective was to develop a comprehensive deep learning assisted radiomics model for assessing not only overall survival in LGG, but also the likelihood of future malignancy and glioma growth velocity. Thus, we retrospectively included 349 LGG patients to develop a prediction model using clinical, anatomical, and preoperative MRI data. Before performing radiomics analysis, a U2-model for glioma segmentation was utilized to prevent bias, yielding a mean whole tumor Dice score of 0.837. Overall survival and time to malignancy were estimated using Cox proportional hazard models. In a postoperative model, we derived a C-index of 0.82 (CI 0.79-0.86) for the training cohort over 10 years and 0.74 (Cl 0.64-0.84) for the test cohort. Preoperative models showed a C-index of 0.77 (Cl 0.73-0.82) for training and 0.67 (Cl 0.57-0.80) test sets. Our findings suggest that we can reliably predict the survival of a heterogeneous population of glioma patients in both preoperative and postoperative scenarios. Further, we demonstrate the utility of radiomics in predicting biological tumor activity, such as the time to malignancy and the LGG growth rate

Morphological and biochemical changes in the mesial temporal lobe in temporal lobe epilepsy

Die GABAerge Neurotransmission im Mandelkern spielt bei der Verarbeitung von emotionalen Prozessen wie Angst, Stress und Belohnung, aber auch für das Gedächtnis, Abhängigkeitserkrankungen und Epilepsie eine wichtige Rolle. Unterschiede in der Verteilung und der Zusammensetzung von GABAA Rezeptoren zwischen verschiedenen Spezies kann die beobachteten Abweichungen von Wirkung und Nebenwirkungen von GABAergen Substanzen erklären. Daten zur Verteilung im humanen Gehirn sind lückenhaft, vor allem im Mandelkern. Daher wird in dieser Studie die Expression der GABAA Rezeptoruntereinheiten 1, 2, 3, 5, 2, 2/3 und 2 in humanen Mandelkernen mittels Immunhistochemie untersucht. Hippocampus-Präparate wurden als Referenzstruktur analysiert. Die Nervenzelldichte und Field Fraction Analyse wurden quantitativ ausgewertet, während die subzelluläre Expression der verschiedenen Untereinheiten semiquantitativ ausgewertet wurde. Die höchste Expressionsdichte der 1 Untereinheit konnte im Lateralkern (La) gezeigt werden, während die 3 Untereinheit in den interkalierten Kernen (IC) prominent exprimiert war. Die 5 und 2 Untereinheiten waren in den kortikalen Kernen (Co) sowie in der amygdalo-hippocampalen und parahippocampal-amygdalären Übergangszone (PHA/AHi) betont. Im Hippocampus zeigten sich die 1 und 3 Untereinheiten im Gyrus dentatus (DG), der CA1 Region und dem Subiculum akzentuiert, während die 5 Untereinheit in allen Subregionen gleichartig exprimiert war. Die 2 Untereinheit war sowohl im Mandelkern als auch dem Hippocampus sehr homogen verteilt, und bei den zwei sowie die 2 Untereinheiten konnte nur eine leichte Immunreaktion beobachtet werden. Die Intensität der Expression der verschiedenen Untereinheiten variierte auch im Neuropil, den Zellkörpern sowie den Dendriten in den verschiedenen Subregionen. GABAA Rezeptoren, welche die 1 Untereinheit mit starker Expression im La, und die 3 Untereinheit mit starker Expression in den IC und dem Subiculum, könnten Zielstrukturen für die Behandlung von Erkrankungen sein, an denen der Mandelkern beteiligt ist. Unterschiede in der Verteilung und Expression von GABAA Rezeptor Untereinheiten zwischen dem Menschen und Nagetieren sollten in der Interpretation von Forschungsergebnissen und bei der Entwicklung von Substanzen, die an Rezeptoren mit bestimmten Untereinheiten, binden, unbedingt bedacht werden. Die Amygdala wird schon lange als zentrale Struktur in der Pathophysiologie der Temporallappenepilepsie betrachtet. Dennoch ist das Wissen über ihre Rolle bei dieser Erkrankung sowie die morphologischen und funktionellen Veränderungen im Vergleich zum Hippocampus gering. Im Tiermodell ist sie eine der für elektrisches Kindling empfindlichsten Strukturen für die Anfallsgenerierung. Ihre Kerne weisen eine hohe Zahl an Verbindungen untereinander auf und stehen auch mit dem Hippocampus sowie anderen corticalen und subcorticalen Strukturen teilweise über den entorhinalen Cortex in Verbindung. Bis dato wurden Veränderungen der GABAA-Rezeptor-Expression nur im Tiermodell der TLE beschrieben, im menschlichen Gehirn vorwiegend im Hippocampus. Die Expression der GABAA- Rezeptor-Untereinheiten 1, 2, 3, 5, 2, 2/3, und 2 wurde mittels Immunhistochemie in 12 Operationspräparaten von Patienten mit TLE, welche den Mandelkern und den angeschlossenen entorhinalen Cortex enthielten, und 12 Autopsiekontrollen ohne bekannte neurologische Vorerkrankung untersucht. Die Expression der Untereinheiten wurde mittels Field-Fraction Analyse quantifiziert, und die subzelluläre Expression an Somata, Dendriten und im Neuropil wurde semiquantitativ evaluiert. In vorliegender Studie konnte ein signifikanter Abfall der Expression der Untereinheiten 1, 2, 3, and 2/3 im Mandelkern bei TLE gezeigt werden. Gleichzeitig stieg die Expression der 2 Untereinheit in den meisten Unterkernen an. Im entorhinalen Cortex zeigte sich eine Reduktion der Expression sämtlicher GABAA-Rezeptor-Untereinheiten außer 1, die an den Zellkörpern verstärkt exprimiert wurde. Die beobachtete generelle Reduktion der Expression von -Untereinheiten könnte zu einer signifikanten Reduktion der Sensitivität des Gewebes gegenüber GABA und verwandten Liganden führen und damit die phasische Hemmung an GABAergen Interneuronen und Primärneuronen negativ beeinflussen. Die erhöhte Expression der 2-Untereinheit spricht für eine gestörte tonische Inhibition. Die Beschreibung dieser Veränderungen im Mandelkern des menschlichen Gehirns stellt eine wichtige Ergänzung im Verständnis der komplexen Veränderungen bei der TLE dar und kann bei der Entwicklung von Medikamenten, die auf Rezeptoren, die aus speziellen Untereinheiten zusammengesetzt sind, wirken, unterstützen. Die Temporallappenepilepsie ist die häufigste Epilepsieform im Erwachsenenalter. Ungefähr die Hälfte der Patienten spricht im Lauf der Erkrankung nicht mehr auf antikonvulsive Medikamente an. Für diese ist Epilepsiechirurgie, bei der die epileptogene Zone chirurgisch entfernt wird, oft eine gute Therapieoption. Die histopathologische Diagnostik basiert auf der ILAE Klassifikation, welche vier unterschiedliche Typen der Ammonshornsklerose kennt. Diese stehen jeweils mit unterschiedlichem epileptologischem Langzeit-Outcome in Zusammenhang. Ziel dieser Studie war es daher, nicht invasiv aufgenommene, hochauflösende, morphologische MR Bilder, welche auf einem Ultrahochfeld Scanner mit 7 Tesla bei Patienten mit TLE präoperativ aufgezeichnet wurden, mit den histopathologischen Ergebnissen postoperativ zu vergleichen. Bei 14 Patienten mit therapieresistenter TLE wurden hochauflösende T2-gewichtete FSE MR Bilder auf einem 7 Tesla Magnetom mit einem 32-Kanal Coil gewonnen. Vier unabhängige Untersucher legten die Grenzen der hippocampalen Subfelder CA1-CA4 fest und evaluierten semiquantitativ deren Volumen, Signalintensität, interne Architektur und allgemeines Grading. Weiters wurde die Sichtbarkeit der Körnerzellschicht des Gyrus dentatus (DGCL) beurteilt. Die Ergebnisse wurden mit der semiquantitativen Beurteilung des Nervenzellverlusts sowie der Astrogliose aus histologischen Schnitten der chirurgischen Präparate verglichen. 7T MR Bilder waren von insgesamt 13 Patienten verfügbar. Volumsverlust, Signalintensität und allgemeines Grading wiesen eine starke Korrelation zwischen MR und Histologie in den einzelnen CA Regionen auf. Pathologische Veränderungen in den CA Subfeldern wurden mit einer Sensitivität und Spezifität von bis zu 100% detektiert. Die Vorhersage des richtigen AHS-Typs war bei 12 von 13 Fällen korrekt. Die Körnerzellschicht des Gyrus dentatus konnte mittels MR nicht dargestellt werden. Hochauflösende, Ultrahochfeld-Magnetresonanz ist ein vielversprechendes Instrument um auch nur geringe Veränderungen im Hippocampus von TLE Patienten zu detektieren. Um den prädiktiven Wert von 7T MRI in der präoperativen Evaluierung von TLE Patienten definieren zu können, wird die Untersuchung von größeren Patientenkohorten erforderlich sein.GABAergic neurotransmission in the amygdala contributes to the regulation of emotional processes in anxiety, stress, reward, mnestic functions, addiction, and epilepsy. Species-specific differences in the distribution and composition of GABAA receptors may account for distinct effects and side-effects of GABAergic agents. However, data on the distribution and composition of GABAA receptors in the human amygdala are lacking. Here, the expression of GABAA receptor subunits 1, 2, 3, 5, 2, 2/3 and 2 was studied in the human amygdala using immunohistochemistry. Hippocampi were evaluated as a reference structure. Neuronal counts and field fraction analyses were performed, and subcellular expression of GABAA receptor subunits was analyzed semiquantitatively. In the amygdala, field fraction analyses showed the highest 1 expression in the lateral nucleus (La), whereas 3 was prominent in intercalated nuclei (IC), and 5 and 2 in the cortical nuclei, and amygdalo-hippocampal/parahippocampal-amygdala transition areas. In the hippocampus, 1 and 3 were accentuated in the dentate gyrus, CA1 region, and subiculum, whereas 5 expression was rather uniform. In both regions, 2 was homogenously distributed, and the two subunits and 2 showed faint immunostaining. The intensity of subunit expression also varied in the neuropil, neuronal somata and/or cellular processes in the subregions. GABAA receptors containing subunit 1, showing the strongest expression in the La, and 3, with the strongest expression in the IC and subiculum, could be targets for treating amygdala-related disorders. Differences in GABAA receptor subunit expression between the human and rodent amygdala should be taken into consideration when developing subunit-selective drugs. The amygdala has long been implicated in the pathophysiology of human temporal lobe epilepsy (TLE). Nevertheless, knowledge on its role in this disease and underlying structural and functional changes are scarce when compared to the hippocampal formation. In rodent models, it is among the brain regions most susceptible to electrical kindling. The different nuclei of this complex structure are interconnected and share reciprocal connections with the hippocampus and other brain structures, partly via the entorhinal cortex. However, changes in GABAA receptor subunit expression in TLE were only studied in animal models, and in the human hippocampus. Expression of GABAA receptor subunits 1, 2, 3, 5, 2, 2/3, and 2 was evaluated by immunohistochemistry in amygdala specimens and the adjacent entorhinal cortex of 12 patients undergoing epilepsy surgery and 12 neurologically intact autopsy controls. Subunit expression was quantified by field fraction analysis, and subcellular expression was semiquantitatively evaluated. A significant decrease in the expression of 1, 2, 3, and 2/3 subunits was found in the amygdala of TLE cases, accompanied by an increase of 2 subunit expression in many nuclei. In the Ent, the expression of all GABAA receptor subunits was decreased except for the 1 subunit, which was increased on cellular somata. The overall reduction in subunit expression may lead to decreased sensitivity to GABA and its ligands and compromise phasic inhibition on GABAergic cells, whereas upregulation of the 2 subunit might influence clustering and kinetics of receptors and impair tonic inhibition. The description of these alterations in the human amygdala is important for the understanding of network changes in TLE as well as the development of subunit-specific therapeutic agents for the treatment of this disease. Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsy in adults. Since about half of these patients develop drug resistance, epilepsy surgery designed to remove the epileptogenic zone is an excellent option in selected patients. Histopathological analyses of hippocampal specimens in TLE patients revealed four types of Ammons horn sclerosis, which are correlated with long-term epileptological outcome. The aim of this study was the correlation of noninvasive, high-resolution, morphological MR imaging at an ultra-high-field (7 Tesla) of the hippocampus in TLE patients with histopathological findings. High-resolution, T2-weighted FSE MR imaging in 14 patients with drug-resistant temporal lobe epilepsy was performed on a 7 Tesla Magnetom using a 32-channel coil. Four independent investigators assessed the delineation and semi-quantitative evaluation of volume, signal intensity, internal architecture, and overall grading of the hippocampal subfields CA1-4, as well as the presence of the dentate granule cell layer (DGCL), on MR images. Results were compared with semi-quantitative evaluation of neuronal loss and astrogliosis in the histological sections of the surgical specimens. 7 T MR examinations were evaluable in 13 cases. Volume loss and signal intensity, as well as overall grading, showed a strong correlation between MRI and histology in individual CA regions. Furthermore, sensitivity and specificity values up to 100% were found for the detection of pathology in the CA subfields. The prediction of AHS type was correct in up to 12 of 13 cases, while the dentate gyrus could not be delineated on MRI. High-resolution, ultra-high-field MR imaging is a promising tool for the detection of subtle changes in the hippocampus in patients with temporal lobe epilepsy. Large cohorts will be necessary to confirm the predictive value of 7T MRI in the preoperative evaluation of TLE patients.submitted by Harald StefanitsAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersMedizinische Universität Wien, Diss., 2018(VLID)353099

EpCAM (CD326) is differentially expressed in craniopharyngioma subtypes and Rathke’s cleft cysts

The epithelial cell adhesion molecule (EpCAM) is a type I glycoprotein located on the surface of epithelial cells. It is strongly expressed in many neoplasms and already used in the diagnosis and distinction of various tumour subtypes. Comparative studies about EpCAM expression in cystic sellar lesions are lacking. Therefore, we analysed its distribution pattern in adamantinomatous (aCP) and papillary (pCP) craniopharyngiomas (CP) and Rathke’s Cleft Cysts (RCC) using immunohistochemistry and gene expression profiling. Whereas the protein was not detectable in pCP (n = 10), all aCP (n = 64) showed distinct staining patterns. The vast majority of RCC (n = 10) also appeared positive, but these displayed notably lower labeling scores. Additionally, significantly higher mRNA levels were detectable in aCP (n = 19) when compared to pCP (n = 10) (p = 9.985−8). Furthermore, pediatric aCP cases, in general, exhibited stronger EpCAM staining levels compared to adult ones (p = 0.015). However, we were not able to verify this result on mRNA level. In summary, our findings demonstrate that EpCAM can be used as an additional distinction-marker for cystic lesions of the sellar region. Its unknown function in aCP and the presence of an approved monoclonal bispecific trifunctional antibody for cancer therapy are interesting starting points for further studies

Seven-Tesla MRI of Hippocampal Sclerosis: An In Vivo Feasibility Study With Histological Correlations.

INTRODUCTION Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsy in adults. Because approximately half of these patients develop drug resistance, epilepsy surgery designed to remove the epileptogenic zone is an excellent option in selected patients. Histopathological analyses of hippocampal specimens in TLE patients revealed 4 types of Ammon's horn sclerosis, which are correlated with long-term epileptological outcome. The aim of this study was the correlation of noninvasive, high-resolution, morphological magnetic resonance imaging (MRI) at an ultra-high-field (7 T) of the hippocampus in TLE patients with histopathological findings. METHODS High-resolution, T2-weighted FSE MRI in 14 patients with drug-resistant temporal lobe epilepsy was performed on a 7-T Magnetom using a 32-channel coil. Four independent investigators assessed the delineation and semiquantitative evaluation of volume, signal intensity, internal architecture, and overall grading of the hippocampal subfields CA1-4, as well as the presence of the dentate granule cell layer (DGCL), on MRI scans. Results were compared with semiquantitative evaluation of neuronal loss and astrogliosis in the histological sections of the surgical specimens. RESULTS Seven-tesla MR examinations were evaluable in 13 cases. Volume loss and signal intensity, as well as overall grading, showed a strong correlation between MRI and histology in individual CA regions. Furthermore, sensitivity and specificity values up to 100% were found for the detection of pathology in the CA subfields. The prediction of Ammon's horn sclerosis type was correct in up to 12 of 13 cases, whereas the dentate gyrus could not be delineated on MRI. DISCUSSION High-resolution, ultra-high-field MRI is a promising tool for the detection of subtle changes in the hippocampus in patients with temporal lobe epilepsy. Large cohorts will be necessary to confirm the predictive value of 7-T MRI in the preoperative evaluation of TLE patients

Expression of SRY-related HMG Box Transcription Factors (Sox) 2 and 9 in Craniopharyngioma Subtypes and Surrounding Brain Tissue

Stem cells have been discovered as key players in the genesis of different neoplasms including craniopharyngioma (CP), a rare tumour entity in the sellar region. Sox2 and Sox9 are well-known stem cell markers involved in pituitary development. In this study we analysed the expression of both transcription factors using immunohistochemistry in a large cohort of 64 adamantinomatous (aCP) and 9 papillary CP (pCP) and quantitative PCR in 26 aCP and 7 pCP. Whereas immunohistochemically Sox2+ cells were verifiable in only five aCP (7.8%) and in 39.1% of the respective surrounding cerebral tissue, pCP specimens appeared always negative. In contrast, Sox9 was detectable in all tumours with a significantly higher expression in aCP compared to pCP (protein, p < 0.0001; mRNA p = 0.0484) This was also true for the respective tumour adjacent CNS where 63 aCP (98.4%) and six pCP (66.7%) showed Sox9+ cells. We further confirmed absence of Sox9 expression in nuclear β-catenin accumulating cells of aCP. Our results point to the conclusion that Sox2 and Sox9, seem to play essential roles not only in the specific formation of aCP, but also in processes involving the cerebral tumour environment, which needs to be illuminated in the future

Cortical and Subcortical Anatomy of the Orbitofrontal Cortex: A White Matter Microfiberdissection Study and Case Series

BACKGROUND The literature on white matter anatomy underlying the human orbitofrontal cortex (OFC) is scarce in spite of its relevance for glioma surgery. OBJECTIVE To describe the anatomy of the OFC and of the underlying white matter fiber anatomy, with a particular focus on the surgical structures relevant for a safe and efficient orbitofrontal glioma resection. Based on anatomical and radiological data, the secondary objective was to describe the growth pattern of OFC gliomas. METHODS The study was performed on 10 brain specimens prepared according to Klingler's protocol and dissected using the fiber microdissection technique modified according to U.T., under the microscope at high magnification. RESULTS A detailed stratigraphy of the OFC was performed, from the cortex up to the frontal horn of the lateral ventricle. The interposed neural structures are described together with relevant neighboring topographic areas and nuclei. Combining anatomical and radiological data, it appears that the anatomical boundaries delimiting and guiding the macroscopical growth of OFC gliomas are as follows: the corpus callosum superiorly, the external capsule laterally, the basal forebrain and lentiform nucleus posteriorly, and the gyrus rectus medially. Thus, OFC gliomas seem to grow ventriculopetally, avoiding the laterally located neocortex. CONCLUSION The findings in our study supplement available anatomical knowledge of the OFC, providing reliable landmarks for a precise topographical diagnosis of OFC lesions and for perioperative orientation. The relationships between deep anatomic structures and glioma formations described in this study are relevant for surgery in this highly interconnected area

Machine learning based outcome prediction of microsurgically treated unruptured intracranial aneurysms

Abstract Machine learning (ML) has revolutionized data processing in recent years. This study presents the results of the first prediction models based on a long-term monocentric data registry of patients with microsurgically treated unruptured intracranial aneurysms (UIAs) using a temporal train-test split. Temporal train-test splits allow to simulate prospective validation, and therefore provide more accurate estimations of a model’s predictive quality when applied to future patients. ML models for the prediction of the Glasgow outcome scale, modified Rankin Scale (mRS), and new transient or permanent neurological deficits (output variables) were created from all UIA patients that underwent microsurgery at the Kepler University Hospital Linz (Austria) between 2002 and 2020 (n = 466), based on 18 patient- and 10 aneurysm-specific preoperative parameters (input variables). Train-test splitting was performed with a temporal split for outcome prediction in microsurgical therapy of UIA. Moreover, an external validation was conducted on an independent external data set (n = 256) of the Department of Neurosurgery, University Medical Centre Hamburg-Eppendorf. In total, 722 aneurysms were included in this study. A postoperative mRS > 2 was best predicted by a quadratic discriminant analysis (QDA) estimator in the internal test set, with an area under the receiver operating characteristic curve (ROC-AUC) of 0.87 ± 0.03 and a sensitivity and specificity of 0.83 ± 0.08 and 0.71 ± 0.07, respectively. A Multilayer Perceptron predicted the post- to preoperative mRS difference > 1 with a ROC-AUC of 0.70 ± 0.02 and a sensitivity and specificity of 0.74 ± 0.07 and 0.50 ± 0.04, respectively. The QDA was the best model for predicting a permanent new neurological deficit with a ROC-AUC of 0.71 ± 0.04 and a sensitivity and specificity of 0.65 ± 0.24 and 0.60 ± 0.12, respectively. Furthermore, these models performed significantly better than the classic logistic regression models (p  2, a pre- and postoperative difference in mRS > 1 point and a GOS < 5. Therefore, generalizability of the models could not be demonstrated in the external validation. A SHapley Additive exPlanations (SHAP) analysis revealed that this is due to the most important features being distributed quite differently in the internal and external data sets. The implementation of newly available data and the merging of larger databases to form more broad-based predictive models is imperative in the future

Risks and Benefits of Glioblastoma Resection in Older Adults : A Retrospective Austrian Multicenter Study

OBJECTIVE: To assess the prognostic profile, clinical outcome, treatment-associated morbidity, and treatment burden of elderly patients with glioblastoma (GBM) undergoing microsurgical tumor resection as part of contemporary treatment algorithms. METHODS: We retrospectively identified patients with GBM >= 65 years of age who were treated by resection at 2 neuro-oncology centers. Survival was assessed by Kaplan-Meier analyses; log-rank tests identified prognostic factors. RESULTS: The study population included 160 patients (mean age, 73.1 +/- 5.1 years), and the median contrastenhancing tumor volume was 31.0 cm(3). Biomarker analyses revealed 0(6)-methylguanine-DNA methyltransferase-promoter methylation in 62.7% and wild-type isocitrate dehydrogenase in 97.5% of tumors. The median extent of resection (EOR) was 92.3%, surgical complications were noted in 10.0% of patients, and the median postoperative hospitalization period was 8 days. Most patients (60.0%) received adjuvant radio-/chemotherapy. The overall treatment-associated morbidity was 30.6%. The median progression-free and overall survival were 5A months (95% confidence interval [Cl], 4.6-6.4 months) and 10.0 months (95% CI, 7.9-11.7 months). The strongest predictors for favorable outcome were patient age = 80% (P = 0.0179), postoperative modified Rankin Scale score CONCLUSIONS: Clinical outcome for elderly patients with GBM remains limited. Nonetheless, the observed treatment-associated morbidity and treatment burden were moderate in the patients, and patient age and performance status remained the strongest predictors for survival. The risks and benefits of tumor resection in the age of biomarker-adjusted treatment concepts require further prospective evaluation.Peer reviewe