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Purpose: Mesenchymal stromal cells (MSCs) within the glioblastoma microenvironment have been shown to promote tumor progression. Tumor Treating Fields (TTFields) are alternating electric fields with low intensity and intermediate frequency that exhibit anti-tumorigenic effects. While the effects of TTFields on glioblastoma cells have been studied previously, nothing is known about the influence of TTFields on MSCs., Methods: Single-cell RNA sequencing and immunofluorescence staining were employed to identify glioblastoma-associated MSCs in patient samples. Proliferation and clonogenic survival of human bone marrow-derived MSCs were assessed after TTFields in vitro. MSC' characteristic surface marker expression was determined using flow cytometry, while multi-lineage differentiation potential was examined with immunohistochemistry. Apoptosis was quantified based on caspase-3 and annexin-V/7-AAD levels in flow cytometry, and senescence was assessed with ß-galactosidase staining. MSCs' migratory potential was evaluated with Boyden chamber assays., Results: Single-cell RNA sequencing and immunofluorescence showed the presence of glioblastoma-associated MSCs in patient samples. TTFields significantly reduced proliferation and clonogenic survival of human bone marrow-derived MSCs by up to 60% and 90%, respectively. While the characteristic surface marker expression and differentiation capacity were intact after TTFields, treatment resulted in increased apoptosis and senescence. Furthermore, TTFields significantly reduced MSCs' migratory capacity., Conclusion: We could demonstrate the presence of tumor-associated MSCs in glioblastoma patients, providing a rationale to study the impact of TTFields on MSCs. TTFields considerably increase apoptosis and senescence in MSCs, resulting in impaired survival and migration. The results provide a basis for further analyses on the role of MSCs in glioblastoma patients receiving TTFields., (© 2024. The Author(s).)

Purpose: PET using radiolabeled amino acid [ 18 F]-fluoro-ethyl- L -tyrosine (FET-PET) is a well-established imaging modality for glioma diagnostics. The biological tumor volume (BTV) as depicted by FET-PET often differs in volume and location from tumor volume of contrast enhancement (CE) in MRI. Our aim was to investigate whether a gross total resection of BTVs defined as < 1 cm 3 of residual BTV (PET GTR) correlates with better oncological outcome., Methods: We retrospectively analyzed imaging and survival data from patients with primary and recurrent WHO grade III or IV gliomas who underwent FET-PET before surgical resection. Tumor overlap between FET-PET and CE was evaluated. Completeness of FET-PET resection (PET GTR) was calculated after superimposition and semi-automated segmentation of pre-operative FET-PET and postoperative MRI imaging. Survival analysis was performed using the Kaplan-Meier method and the log-rank test., Results: From 30 included patients, PET GTR was achieved in 20 patients. Patients with PET GTR showed improved median OS with 19.3 compared to 13.7 months for patients with residual FET uptake (p = 0.007; HR 0.3; 95% CI 0.12-0.76). This finding remained as independent prognostic factor after performing multivariate analysis (HR 0.19, 95% CI 0.06-0.62, p = 0.006). Other survival influencing factors such as age, IDH-mutation, MGMT promotor status, and adjuvant treatment modalities were equally distributed between both groups., Conclusion: Our results suggest that PET GTR improves the OS in patients with WHO grade III or IV gliomas. A multimodal imaging approach including FET-PET for surgical planning in newly diagnosed and recurrent tumors may improve the oncological outcome in glioma patients., (© 2021. The Author(s).)

Background: Glioblastoma of the corpus callosum (ccGBM) are rare tumors, with a dismal prognosis marked by a rapid clinical deterioration. For a long time, surgical treatment was not considered beneficial for most patients with such tumors. Recent studies claimed an improved survival for patients undergoing extensive resection, albeit without integration of the molecular profile of the lesions. The purpose of this study was to investigate the effect of biopsy and surgical resection on oncological and functional outcomes in patients with IDH wild-type ccGBM., Methods: We performed a retrospective analysis of our institution's database of patients having been treated for high-grade glioma between 2005 and 2017. Inclusion criteria were defined as follows: patients older than 18 years, histopathological, and molecularly defined IDH wild-type glioma, major tumor mass (at least 2/3) invading the corpus callosum in the sagittal plane with a uni- or bilateral infiltration of the adjacent lobules. Surgical therapy (resection vs. biopsy), extent of resection according to the remaining tumor volume and adjuvant treatment as well as overall survival and functional outcome using the Karnofsky Performance Score (KPS) were analyzed., Results: Fifty-five patients were included in the study, from which the mean age was 64 years and men (n = 34, 61.8%) were more often affected than women (n = 21, 38.2%). Thirty (54.5%) patients were treated with stereotactic biopsy alone, while 25 patients received tumor resection resulting in 14.5% (n = 8) gross-total resections and 30.9% (n = 17) partial resections. The 2-year survival rate after resection was 30% compared to 7% after biopsy (p = 0.047). The major benefit was achieved in the group with gross-total resection, while partial resection failed to improve survival. Neurological outcome measured by KPS did not differ between both groups either pre- or postoperatively., Conclusions: Our study suggests that in patients with corpus callosum glioblastoma, gross-total resection prolongs survival without negatively impacting neurological outcome as compared to biopsy.

Introduction: Elderly patients constitute an expanding part of our society. Due to a continuously increasing life expectancy, an optimal quality of life is expected even into advanced age. Glioblastoma (GBM) is more common in older patients, but they are still often withheld from efficient treatment due to worry of worse tolerance and have a significantly worse prognosis compared to younger patients. Our retrospective observational study aimed to investigate the therapeutic benefit from a second resection in recurrent glioblastoma of elderly patients., Materials and Methods: We included a cohort of 39 elderly patients (> 65 years) with a second resection as treatment option in the case of a tumor recurrence. A causal inference model was built by multiple non- and semiparametric models, which was used to identify matched patients from our elderly GBM database which comprises 538 patients. The matched cohorts were analyzed by a Cox-regression model adjusted by time-dependent covariates., Results: The Cox-regression analysis showed a significant survival benefit (Hazard Ratio: 0.6, 95% CI 0.36-0.9, p-value = 0.0427) for the re-resected group (18.0 months, 95% CI 13.97-23.2 months) compared to the group without re-resection (10.1 months, 95% CI 8.09-20.9 months). No differences in the co-morbidities or hemato-oncological side effects during chemotherapy could be detected. Anesthetic- and surgical complications were rare and comparable to the complication rate of patients undergoing the first-line resection., Conclusion: Taken together, in elderly patients, re-resection is an acceptable treatment option in the recurrent state of a glioblastoma. The individual evaluation of the patients' medical status as well as the chances of withstanding general anesthesia needs to be done in close interdisciplinary consultation. If these requirements are met, elderly patients benefit from a re-resection.

Purpose: To provide detailed long-term data after initial observation for patients after histological confirmation of low grade (WHO II) gliomas according to molecular stratification., Methods: A series of 110 patients with watchful waiting strategy after initial surgery for LGG and re-surgery at tumor progression were analyzed. Progression-free survival, time to malignant transformation, post-recurrence survival, and overall survival were estimated with the Kaplan-Meier method. Prognostic factors were identified by the Log Rank test and Cox multivariate proportional hazards model., Results: The cohort comprised 18 IDH wild type (IDH wt ) and 53 IDH mutated (IDH mut ) astrocytomas, and 39 IDH mutated and 1p 19q co-deleted (IDH mut/codel ) patients. The median follow-up was 126 (95% CI 109-143) months. Surgery was gross total resection in 58, subtotal resection in 28, and biopsy in 24 patients. Progression-free survival rates at 5, 10 and 15 years was 38% 18% and 1%. The corresponding malignant transformation rates were 17%, 39% and 71%. The initial extent of resection influenced progression-free survival, time to malignant transformation and overall survival. Molecular subtype IDH mut/codel was the strongest prognostic factor for overall survival and for time to malignant transformation., Conclusion: The strongest determinant of the patients' course after initial watchful waiting was the molecular tumor status. Extensive resection may increase time to progression and malignant transformation. Observation may be justified in selected patients.

Purpose: According to the 2016 WHO classification lower-grade gliomas consist of three groups: IDH-mutated and 1p/19q co-deleted, IDH-mutated and IDH-wildtype tumors. The aim of this study was to evaluate the impact of surgical therapy for lower-grade gliomas with a particular focus on the molecular subgroups., Methods: This is a bi-centric retrospective analysis including 299 patients, who underwent treatment for lower-grade glioma between 1990 and 2016. All tumors were re-classified according to the 2016 WHO classification. Data concerning baseline and tumor characteristics, overall survival, different treatment modalities and functional outcome were analyzed., Results: A total of 112 (37.5%) patients with IDH-mutation and 1p/19q co-deletetion, 86 (28.8%) patients with IDH-mutation and 101 (33.8%) patients with IDH-wildtype tumors were identified. The median overall survival (mOS) differed significantly between the groups (p < 0.001). Surgical resection was performed in 226 patients and showed significantly improved mOS compared to the biopsy group (p = 0.001). Gross total resection (GTR) was associated with better survival (p = 0.007) in the whole cohort as well as in the IDH-mutated and IDH-wildtype groups compared to partial resection or biopsy. IDH-wildtype patients presented a significant survival benefit after combined radio-chemotherapy compared to radio- or chemotherapy alone (p = 0.02). Good clinical status (NANO) was associated with longer OS (p = 0.001)., Conclusion: The impact of surgical treatment on the outcome of lower-grade gliomas depends to a great extent on the molecular subtype of the tumors. Patients with more aggressive tumors (IDH-wildtype) seem to profit from more intensive treatment like GTR, multiple resections and combined radio-/chemotherapy.

Introduction: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults with peak incidence in patients older than 65 years. These patients are mostly underrepresented in clinical trials and often undertreated due to concomitant diseases. Recently, different therapeutic approaches for elderly patients with GBM were discussed. To date, there is no defined standard treatment. The aim of the present study is to evaluate the functional and oncological outcome in surgical treatment of elderly patients., Materials and Methods: A total of 342 elderly patients aged ≥ 65 years were retrospectively analyzed in our neurosurgical center. Surgical therapy, adjuvant treatment, overall survival (OS) and functional outcome using Karnofsky performance scale (KPS) and Neurological assessment of neuro-oncology-score were analyzed., Results: The median age at GBM diagnosis was 73.4 (IQR 9.28) years. Median overall survival was 7.5 (CI 95% 6.0-9.1) months and median preoperative or postoperative KPS was 80 (IQR 20). Surgical resection was performed in 216 (63.2%) patients, in 125 patients (36.5%) patients a stereotactic biopsy was performed. The median OS was significantly higher in patients with gross total resection (GTR) compared to partial resection and biopsy (10.8 months; CI 95% 9.5-12.3). Patients with combined radio- and chemo-therapy (RCT) showed significant longer OS, particularly MGMT-negative GBM. Higher preoperative KPS was found to be associated with improved overall survival., Conclusion: GTR and adjuvant combined RCT provides benefits for overall survival in elderly patients. Therapy decision should be made in regard to preoperative functional status instead of biological age.

Background: The purpose of this study is to map spatial metabolite differences across three molecular subgroups of glial tumors, defined by the IDH1/2 mutation and 1p19q-co-deletion, using magnetic resonance spectroscopy. This work reports a new MR spectroscopy based classification algorithm by applying a radiomics analytics pipeline., Materials: 65 patients received anatomical and chemical shift imaging (5 × 5 × 20 mm voxel size). Tumor regions were segmented and registered to corresponding spectroscopic voxels. Spectroscopic features were computed (n = 860) in a radiomic approach and selected by a classification algorithm. Finally, a random forest machine-learning model was trained to predict the molecular subtypes., Results: A cluster analysis identified three robust spectroscopic clusters based on the mean silhouette widths. Molecular subgroups were significantly associated with the computed spectroscopic clusters (Fisher's Exact test p < 0.01). A machine-learning model was trained and validated by public available MRS data (n = 19). The analysis showed an accuracy rate in the Random Forest model by 93.8%., Conclusions: MR spectroscopy is a robust tool for predicting the molecular subtype in gliomas and adds important diagnostic information to the preoperative diagnostic work-up of glial tumor patients. MR-spectroscopy could improve radiological diagnostics in the future and potentially influence clinical and surgical decisions to improve individual tumor treatment.

Although atypical meningioma recurs frequently in spite of total resection and/or radiotherapy, no consensus on optimal adjuvant management was found. However, several retrospective studies analysed the additional effect of adjuvant radiotherapy in atypical meningioma with inconsistent results. Therefrom, the purpose of this study was to evaluate prognostic factors influencing the recurrence/progression and progression-free survival (PFS) rates of atypical meningioma, particularly focused on the role of postoperative adjuvant radiotherapy. Between February 2001 and March 2015, 161 atypical meningioma resections were performed in our Department of Neurosurgery, of which, 128 cases underwent surgical treatment alone and 33 cases underwent surgery and radiotherapy. Kaplan-Meier analysis was used to provide median point estimates and PFS rates. The Cox-regression model was used in the univariate and multivariate analysis to identify significant factors associated with treatment. The extent of resection (Simpson grade I and II) significantly influenced the risk of recurrence (hazard ratio = 1.8, CI (95%) 1.3-2.6, p-value = 0.0004). There was no significant benefit for progression-free survival after adjuvant radiotherapy (hazard ratio = 1.48, CI (95%) 0.76-2.86, p-value = 0.22). Additionally, meningioma located at the anterior and posterior fossa showed a significantly longer PFS compared to other locations (p-value = 0.03). Adjuvant postoperative radiotherapy had no significant impact on recurrence/progression rate or PFS. The extent of resection according to Simpson grade remains the most important prognostic factor associated with lower recurrence/progression rates and longer PFS in patients with atypical meningioma. The location of the tumours at the anterior or posterior fossa was an independent factor associated with improved PFS.

Objectives: To differentiate between abnormal tumor vessels and regular brain vasculature using new quantitative measures in time-of-flight (TOF) MR angiography (MRA) data., Materials and Methods: In this work time-of-flight (TOF) MR angiography data are acquired in 11 glioma patients to quantify vessel abnormality. Brain vessels are first segmented with a new algorithm, efficient monte-carlo image-analysis for the location of vascular entity (EMILOVE), and are then characterized in three brain regions: tumor, normal-appearing contralateral brain, and the total brain volume without the tumor. For characterization local vessel orientation angles and the dot product between local orientation vectors are calculated and averaged in the 3 regions. Additionally, correlation with histological and genetic markers is performed., Results: Both the local vessel orientation angles and the dot product show a statistically significant difference (p < 0.005) between tumor vessels and normal brain vasculature. Furthermore, the connection to both histology and the gene expression of the tumor can be found-here, the measures were compared to the proliferation marker Ki-67 [MIB] and genome-wide expression analysis. The results in a subgroup indicate that the dot product measure may be correlated with activated genetic pathways., Conclusion: It is possible to define a measure of vessel abnormality based on local vessel orientation angles which can differentiate between normal brain vasculature and glioblastoma vessels.