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Epilepsy surgery in low-grade epilepsy-associated neuroepithelial tumors (LEAT) is usually evaluated in drug-resistant cases, often meaning a time delay from diagnosis to surgery. To identify factors predicting good postoperative seizure control and neuropsychological outcome, the cohort of LEAT patients treated with resective epilepsy surgery at the Epilepsy Center Frankfurt Rhine-Main, Germany between 2015 and 2020 was analyzed. Thirty-five patients (19 males (54.3%) and 16 females, aged 4 to 40 years (M = 18.1), mean follow-up 33 months) were included. Following surgery, 77.1% of patients remained seizure-free (Engel IA/ILAE 1). Hippocampus and amygdala resection was predictive for seizure freedom in temporal lobe epilepsy. In total, 65.7% of all patients showed cognitive deficits during presurgical workup, decreasing to 51.4% after surgery, predominantly due to significantly less impaired memory functions (p = 0.011). Patients with presurgical cognitive deficits showed a tendency toward a longer duration of epilepsy (p = 0.050). Focal to bilateral tonic-clonic seizures (p = 0.019) and young age at onset (p = 0.018) were associated with a higher likelihood of cognitive deficits after surgery. Therefore, we advocate early epilepsy surgery without requiring proof of drug-resistance. This refers especially to lesions associated with the non-eloquent cortex.

Epilepsy surgery in low-grade epilepsy-associated neuroepithelial tumors (LEAT) is usually evaluated in drug-resistant cases, often meaning a time delay from diagnosis to surgery. To identify factors predicting good postoperative seizure control and neuropsychological outcome, the cohort of LEAT patients treated with resective epilepsy surgery at the Epilepsy Center Frankfurt Rhine-Main, Germany between 2015 and 2020 was analyzed. Thirty-five patients (19 males (54.3%) and 16 females, aged 4 to 40 years (M = 18.1), mean follow-up 33 months) were included. Following surgery, 77.1% of patients remained seizure-free (Engel IA/ILAE 1). Hippocampus and amygdala resection was predictive for seizure freedom in temporal lobe epilepsy. In total, 65.7% of all patients showed cognitive deficits during presurgical workup, decreasing to 51.4% after surgery, predominantly due to significantly less impaired memory functions (

DNA methylation-based tumor classification allows an enhanced distinction into subgroups of glioblastoma. However, the clinical benefit of DNA methylation-based stratification of glioblastomas remains inconclusive. We performed a multicentric cohort study including 430 patients with newly diagnosed glioblastoma whose tumors were subjected to DNA methylation profiling. The primary outcome was overall survival (OS) and progression-free survival (PFS). Secondary outcomes were the prognostic relevance of EOR and MGMTpromoter methylation status as well as surgical benefit for recurrent glioblastoma. After stratifying patients in accordance with their DNA methylation subclasses RTK I, RTK II, and mesenchymal (MES), outcome analyses revealed no significant differences between these three methylation subclasses (p = 0.06). RTK I or RTK II tumors who underwent gross-total resection (GTR) or near GTR had a longer OS and PFS than partially resected patients (p < 0.01). In the MES subclass, no survival benefit for a maximized EOR was found (p = 0.33). In multivariate analysis, the therapy response-predictive value of MGMT promoter methylation was evident for RTK I (p < 0.01) and RTK II (p = 0.02) but failed to be an independent factor in the MES subclass (p= 0.06). For local recurrence, re-resection conveyed a progression-to-overall survival (POS) benefit (p < 0.01), which was evident in the RTK I (p = 0.03) and RTK II (p < 0.01) subclasses, but not in the MES subclass (p = 0.33).This study demonstrates a survival benefit from maximized EOR at surgery for newly diagnosed and recurrent glioblastomas of the RTK I and RTK II subclass but not the MES subclass. Hence, it needs to be carefully considered whether the MES subclass should be treated with maximal surgical resection, especially when located in eloquent areas and at time of recurrence.

The classification of human brain tumors by global DNA methylation profiling has become an essential part of modern integrated neuropathological diagnostics. It has proven to reliably identify known and novel brain tumor (sub-)types that are biologically and clinically distinct. Therefore, this technique has critically improved diagnostic accuracy and risk stratification of brain tumor patients. Although indispensable for the understanding of tumor biology and for preclinical drug trials, the comparison of genetically engineered mouse models to human brain tumors is still difficult. The assessment of tumor morphology only provides an approximate picture, and transcriptomic data from human brain tumors are sparse and suffer from platform-related technical incomparability. Here, we show array-based DNA methylation profiling of well-established murine brain tumors, such as Wnt and Shh medulloblastoma, YAP and RELA ependymoma, ETMR, and AT/RT. Similar to human brain tumors, unbiased clustering methods revealed distinct methylation profiles and mean methylation levels for mouse brain tumors types. Analyses were possible for fresh-frozen as well as for paraffin-embedded tissue, and copy number alterations could be inferred from methylation profiles. Most importantly, first results suggest that inter-species comparisons allow the classification of brain tumors from known or novel mouse models based on the constantly growing spectrum of human brain tumor types and subtypes with hundreds of thousands of available datasets. As an example, upon DNA methylation profiling, cerebellar tumors arising in Math1-cre::SmoM2Fl/+ mice display the highest similarity to human SHH medulloblastoma when compared to multiple human brain tumor entities including WNT and Non-WNT/Non-SHH medulloblastoma. These results suggest that global DNA methylation profiling may add another very important level of information to the characterization of genetically engineered mouse models.

INTRODUCTION: Classification as well as treatment of patients with lower grade gliomas (°II+°III) have changed fundamentally during the last years. Molecular markers have augmented diagnostic workup and combined radiochemotherapy was established for most of the subgroups. However, molecular markers have not been part of the inclusion criteria of most of the relevant clinical trials. Larger analyses outside of clinical trials are rare. MATERIALS AND METHODS: We screened our clinical cancer database for patients with lower grade glioma newly diagnosed from 1995 to 2015. We identified 774 patients of whom 345 had to be excluded, resulting in an evaluable cohort of 423 patients. We evaluated general characteristics, morphological diagnosis, molecular markers, treatment, time-to-treatment-failure (TTF; initiation of a new treatment or death) and overall survival (OS). RESULTS: According to the 2007 WHO classification our cohort included 145 (34.3%) Astrocytoma WHO °II, 56 (13.3%) Oligoastrocytoma/Oligodendroglioma WHO °II, 129 (52.5%) Astrocytoma WHO °III and 93 (22.0%) Oligoastrocytoma/Oligodendroglioma WHO °III. In 235 patients we were able to molecularly classify the tumors based on the 2017 WHO classification using IDH status and 1p/19q or ATRX status. Patients with a molecularly defined Oligodendroglioma showed a median TTF of 5.2, 4.2 and 7.8 years for radiotherapy, chemotherapy and radiochemotherapy, respectively. Patients with a molecularly defined Astrocytoma showed a median TTF of 1.6, 2.9 and 6.7 years for radiotherapy, chemotherapy and radiochemotherapy, respectively. In IDH wildtype tumors TTF was below 12 months without relevant differences. Treatment with combined radiochemotherapy resulted in markedly improve TTF in molecular defined oligodendroglioma and astrocytoma compared with either radiotherapy or chemotherapy alone. Due to the short follow-up of 5.3 years (mean) median OS has not been reached for any of the IDH mutant subgroups. CONCLUSIONS: Combined treatment with radiotherapy and chemotherapy resulted in markedly improved TTF in patients with molecularly defined oligodendroglioma and astrocytoma.

Intracranial subependymomas are rare, mostly asymptomatic tumours, which are often found incidentally and therefore did not receive much attention in previous literature. By being classified as benign grade I in the WHO classification of tumours of the central nervous system, they are given a special status compared to the other ependymal tumours. Tumor recurrences are a rarity, spinal "drop metastases" do not occur. While etiological, pathological and therapeutic characteristics have been subject of several publications over the last few decades and have meanwhile been well studied, the imaging characteristics are much less well received.Retrospective analysis of our relatively large group of 33 patients with subependymoma, including 4 patients with a mixture of subependymomas with ependymal cell fractions in terms of imaging and clinical aspects and with reference to a current literature review.Subependymomas have typical image morphologic characteristics that differentiate them from tumors of other entities, however, the rare subgroup of histopathological mixtures of subependymomas with ependymal cell fractions has no distinctly different imaging properties.Knowing the imaging characteristics of subpendymoma and their differential diagnoses is of particular importance in order to be able to decide between the necessity of follow-up controls, an early invasive diagnosis or, depending on the entity, tumor resection.· Subependymomas have typical imaging characteristics that are clearly distinguishable from other entities.. · Increased incidence in middle/ older aged men, most frequent localization: 4th ventricle.. · Symptomatic subependymomas, often located in lateral ventricles, are usually characterized by hydrocephalus.. · Radiological identification of mixed subependymoma with ependymal cell fractions is not possible.. · Image based differentiation from other entities is important for the procedure..· Kammerer S, Mueller-Eschner M, Lauer A et al. Subependymomas - Characteristics of a "Leave me Alone" Lesion. Fortschr Röntgenstr 2018; 190: 955 - 966.ZIEL: Intrakranielle Subependymome sind seltene, meist asymptomatische Tumore, die oft als Zufallsbefund auffallen und in der Literatur wahrscheinlich aus diesem Grund wenig Beachtung finden. In der WHO-Klassifikation der Tumoren des zentralen Nervensystems mit Grad I als benigne klassifiziert, nehmen sie gegenüber den übrigen ependymalen Tumoren eine Sonderstellung ein. Tumorrezidive sind eine Rarität; spinale Abtropfmetastasen kommen nicht vor. Während ätiologische, pathologische und therapeutische Charakteristika seit Jahrzehnten Gegenstand einiger Publikationen und mittlerweile gut untersucht sind, findet der bildmorphologische Aspekt deutlich weniger Beachtung.Retrospektive Analyse unseres relativ großen institutseigenen Kollektivs von 33 Patienten mit Subependymom einschließlich 4 Patienten mit einer Mischform aus Subependymomen mit ependymalen Zellanteilen hinsichtlich bildgebender und klinischer Aspekte und Bezug auf eine aktuelle Literaturübersicht.Subependymome weisen typische bildmorphologische Charakteristika auf, die sie von Tumoren anderer Entität, nicht aber der seltenen Sonderform eines histopathologischen Mischbildes aus Subependymom- und Ependymomanteilen, unterscheiden.Bildmorphologische Eigenschaften der Subependymome und Differentialdiagnosen zu kennen ist von besonderer Bedeutung, um je nach Entität zwischen Verlaufskontrollen, einer zeitnahen invasiven Abklärung und gegebenenfalls Resektion entscheiden zu können.· Subependymome weisen typische, gegenüber anderen Tumorentitäten klar abgrenzbare bildgebende Charakteristika auf.. · Vermehrtes Auftreten bei Männern mittleren/ höheren Alters, häufigste Lokalisation im 4.Ventrikel.. · Symptomatische Subependymome, häufig im Seitenventrikel lokalisiert, fallen meist durch einen Hydrocephalus auf.. · Die bildmorphologische Differenzierung eines gemischten Subependymoms mit ependymalen Zellanteilen ist nicht möglich.. · Die radiologische Abgrenzung gegenüber anderen Entitäten ist von Bedeutung für das Procedere..· Kammerer S, Mueller-Eschner M, Lauer A et al. Subependymomas – Characteristics of a “Leave me Alone” Lesion. Fortschr Röntgenstr 2018; 190: 955 – 966.