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STUDY DESIGN.: A retrospective clinical analysis of patients operated on for spinal tumors. OBJECTIVE.: To report on the importance of intraoperative neurophysiological monitoring (INM) throughout the entire surgical procedure. SUMMARY OF BACKGROUND DATA.: Postoperative neurological deterioration, despite unaltered neurophysiological monitoring, has been reported. This might be related to timely restricted monitoring. Thus, the likelihood of alterations in INM from positioning to wound closure was analyzed. METHODS.: Two hundred three patients (age range, 54.9 ± 17.4 yr) undergoing intradural tumor removal were sampled in a prospective database and analyzed for the occurrence of alterations in intraoperative somatosensory- and motor-evoked potentials. RESULTS.: INM alterations were observed in 47 of 203 (23.2%) patients. These alterations were related to tumor resection in 29 (14.3%) cases, whereas these were unrelated to tumor removal in 18 patients: laminotomy in 5 (2.5%) patients, dura opening in 7 (3.5%) patients, dura closure in 5 (2.5%) patients, and laminoplasty in 1 (0.5%) patient caused INM changes. CONCLUSION.: This study demonstrates that monitoring beyond tumor resection is of essential importance in order to detect all critical phases of surgical procedure and to counteract accordingly. [ABSTRACT FROM AUTHOR]

Background: Brain metastases (BM) constitute an increasing challenge in oncology due to their impact on neurological function, limited treatment options, and poor prognosis. BM occurs through extravasation of circulating tumor cells across the blood-brain barrier. However, the extravasation processes are still poorly understood. We here propose a brain colonization process which mimics infarction-like microenvironmental reactions, that are dependent on Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)., Methods: In this study, intracardiac BM models were used, and cerebral blood microcirculation was monitored by 2-photon microscopy through a cranial window. BM formation was observed using cranial magnetic resonance, bioluminescent imaging, and postmortem autopsy. Ang-2/VEGF targeting strategies and Ang-2 gain-of-function (GOF) mice were employed to interfere with BM formation. In addition, vascular and stromal factors as well as clinical outcomes were analyzed in BM patients., Results: Blood vessel occlusions by cancer cells were detected, accompanied by significant disturbances of cerebral blood microcirculation, and focal stroke-like histological signs. Cerebral endothelial cells showed an elevated Ang-2 expression both in mouse and human BM. Ang-2 GOF resulted in an increased BM burden. Combined anti-Ang-2/anti-VEGF therapy led to a decrease in brain metastasis size and number. Ang-2 expression in tumor vessels of established human BM negatively correlated with survival., Conclusions: Our observations revealed a relationship between disturbance of cerebral blood microcirculation and brain metastasis formation. This suggests that vessel occlusion by tumor cells facilitates brain metastatic extravasation and seeding, while combined inhibition of microenvironmental effects of Ang-2 and VEGF prevents the outgrowth of macrometastases., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Objective: Treatment for malignant gliomas involves multiple disciplines, including neurosurgery, radiation therapy, medical and neuro-oncology, and palliative medicine, with function-preserving neurosurgical tumor removal being crucial. However, real-world data on hospital cases, treatment types, especially regarding surgical approaches, and the associated complication and mortality rates in Germany are lacking., Methods: We analyzed data on hospital cases involving malignant gliomas (ICD-10-GM code C71) from the German §21 Hospital Remuneration Act, provided by the Institute for the Hospital Remuneration System (InEK GmbH), from 2019 to 2022. Our focus was on neuro-oncological operations defined by the German Cancer Society (DKG) and included specific operation and procedure (OPS) codes., Results: From 2019 to 2022, there were 101,192 hospital cases involving malignant gliomas in Germany. Neurosurgical tumor removal was performed in 27,193 cases (26.9%). Microsurgical techniques were used in 95% of surgeries, intraoperative navigation systems in 84%, fluorescence-guided surgeries in 45.6%, and intraoperative neurophysiological monitoring (IONM) in 46.4%. Surgical or medical complications occurred in 2903 cases (10.7%). The hospital mortality rate was 2.7%. Mortality was significantly higher in patients aged 65 and older (Odds ratio 2.9, p < 0.0001), and lower in cases using fluorescence-guided procedures (Odds ratio 0.8, p = 0.015) and IONM (Odds ratio 0.5, p < 0.0001)., Conclusions: Over the course of 4 years, over 100,000 hospital cases involving adult patients diagnosed with malignant gliomas were treated in Germany, with 27,193 cases undergoing tumor removal using various modern surgical techniques. The hospital mortality rate was 2.7%., (© 2024. The Author(s).)

Purpose: To benchmark palliative care practices in neurooncology centers across Germany, evaluating the variability in palliative care integration, timing, and involvement in tumor board discussions. This study aims to identify gaps in care and contribute to the discourse on optimal palliative care strategies., Methods: A survey targeting both German Cancer Society-certified and non-certified university neurooncology centers was conducted to explore palliative care frameworks and practices for neurooncological patients. The survey included questions on palliative care department availability, involvement in tumor boards, timing of palliative care integration, and use of standardized screening tools for assessing palliative burden and psycho-oncological distress., Results: Of 57 centers contacted, 46 responded (81% response rate). Results indicate a dedicated palliative care department in 76.1% of centers, with palliative specialists participating in tumor board discussions at 34.8% of centers. Variability was noted in the initiation of palliative care, with early integration at the diagnosis stage in only 30.4% of centers. The survey highlighted a significant lack of standardized spiritual care assessments and minimal use of advanced care planning. Discrepancies were observed in the documentation and treatment of palliative care symptoms and social complaints, underscoring the need for comprehensive care approaches., Conclusion: The study highlights a diverse landscape of palliative care provision within German neurooncology centers, underscoring the need for more standardized practices and early integration of palliative care. It suggests the necessity for standardized protocols and guidelines to enhance palliative care's quality and uniformity, ultimately improving patient-centered care in neurooncology., (© 2024. The Author(s).)

Background: Emerging evidence suggests that fasting could play a key role in cancer treatment. Its metabolic effects on gliomas require further investigation., Purpose: To design a multi-voxel 1 H/ 31 P MR-spectroscopic imaging (MRSI) protocol for noninvasive metabolic monitoring of cerebral, fasting-induced changes on an individual patient/tumor level, and to assess its technical reliability/reproducibility., Study Type: Prospective., Population: MRS phantom. Twenty-two patients (mean age = 61, 6 female) with suspected WHO grade II-IV glioma examined before and after 72-hour-fasting prior to biopsy/resection., Field Strength/sequence: 3-T, 1 H decoupled 3D 31 P MRSI, 2D 1 H sLASER MRSI at an echo time of 144 msec, 2D 1 H MRSI (as water reference), T1-weighted, T1-weighted contrast-enhanced, T2-weighted, and FLAIR. sLASER and PRESS sequences were used for phantom measurements., Assessment: Phantom measurements and spectral simulations were performed with various echo-times for protocol optimization. In vivo spectral analyses were conducted using LCModel and AMARES, obtaining quality/fitting parameters (linewidth, signal-to-noise-ratio, and uncertainty measures of fitting) and metabolite intensities. The volume of glioma sub-regions was calculated and correlated with MRS findings. Ex-vivo spectra of necrotic tumor tissues were obtained using high-resolution magic-angle spinning (HR-MAS) technique., Statistical Tests: Wilcoxon signed-rank test, Bland-Altman plots, and coefficient of variation were used for repeatability analysis of quality/fitting parameters and metabolite concentrations. Spearman ρ correlation for the concentration of ketone bodies with volumes of glioma sub-regions was determined. A P-value <0.05 was considered statistically significant., Results: 1 H and 31 P repeatability measures were highly consistent between the two sessions. β-hydroxybutyrate and acetoacetate were detectable (fitting-uncertainty <50%) in glioma sub-regions of all patients who completed the 72-hour-fasting cycle. β-hydroxybutyrate accumulation was significantly correlated with the necrotic/non-enhancing tumor core volume (ρ = 0.81) and validated using ex-vivo 1 H HR-MAS., Data Conclusion: We propose a comprehensive MRS protocol that may be used for monitoring cerebral, fasting-induced changes in patients with glioma., Evidence Level: 1 TECHNICAL EFFICACY: Stage 4., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Glioblastoma (GB) is incurable at present without established treatment options for recurrent disease. In this phase I first-in-human clinical trial we investigated safety and feasibility of adoptive transfer of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2, which is expressed at elevated levels by a subset of glioblastomas., Methods: Nine patients with recurrent HER2-positive GB were treated with single doses of 1 × 107, 3 × 107, or 1 × 108 irradiated CAR-NK cells injected into the margins of the surgical cavity during relapse surgery. Imaging at baseline and follow-up, peripheral blood lymphocyte phenotyping and analyses of the immune architecture by multiplex immunohistochemistry and spatial digital profiling were performed., Results: There were no dose-limiting toxicities, and none of the patients developed a cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Five patients showed stable disease after relapse surgery and CAR-NK injection that lasted 7 to 37 weeks. Four patients had progressive disease. Pseudoprogression was found at injection sites in 2 patients, suggestive of a treatment-induced immune response. For all patients, median progression-free survival was 7 weeks, and median overall survival was 31 weeks. Furthermore, the level of CD8+ T-cell infiltration in recurrent tumor tissue prior to CAR-NK cell injection positively correlated with time to progression., Conclusions: Intracranial injection of HER2-targeted CAR-NK cells is feasible and safe in patients with recurrent GB. 1 × 108 NK-92/5.28.z cells was determined as the maximum feasible dose for a subsequent expansion cohort with repetitive local injections of CAR-NK cells., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Despite advances in gender equality, only 6% of German neurosurgical departments are currently led by women. With regard to their pioneering work and the importance of their role model effect, we aimed at reporting on the career pathways of the present and former female chairs of neurosurgical departments in Germany. We approached current and former female chairs in German neurosurgery and gathered descriptive information on their ways into leadership positions through structured interviews. Data were obtained from 16/22 (72.7%) female neurosurgical chairs, aged between 44 and 82 years. They completed their training within 6.5 ± 0.6 years, and it took them further 14.5 ± 5.9 years between training completion and chair acquisition. Having obtained their chair positions between 1993 and 2020, six (37.5%) of them have retired or changed career tracks. Of ten (62.5%) chairs still practicing, two are directors of university departments. Twelve (75.0%) hold professorships. Nine chairs (56.3%) are married, eight (50.0%) having children. Five chairs reported having experienced gender-based discrimination. Twelve had a male mentor or role model, two had a female role model, while only one had a female mentor. This study characterizes the to date small number of female neurosurgical chairs in Germany and their paths to neurosurgical leadership positions. In future, these should become historical in order to perceive the presence of women in leadership positions as self-evident normality, reflecting our society. However, further analyses comparing paths of both female and male neurosurgical chairs are necessary to explore gender-based differences in achieving neurosurgical leadership positions., (© 2023. The Author(s).)

Background: 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., Methods: Multicentric cohort study including 430 patients with newly diagnosed glioblastoma subjected to global DNA methylation profiling. Outcome measures included overall survival (OS), progression-free survival (PFS), prognostic relevance of EOR and MGMT promoter methylation status as well as a surgical benefit for recurrent glioblastoma., Results: 345 patients (80.2%) fulfilled the inclusion criteria and 305 patients received combined adjuvant therapy. DNA methylation subclasses RTK I, RTK II, and mesenchymal (MES) revealed no significant survival differences (RTK I: Ref.; RTK II: HR 0.9 [95% CI, 0.64-1.28]; p = 0.56; MES: 0.69 [0.47-1.02]; p = 0.06). Patients with RTK I (GTR/near GTR: Ref.; PR: HR 2.87 [95% CI, 1.36-6.08]; p < 0.01) or RTK II (GTR/near GTR: Ref.; PR: HR 5.09 [95% CI, 2.80-9.26]; p < 0.01) tumors who underwent gross-total resection (GTR) or near GTR had a longer OS and PFS than partially resected patients. The MES subclass showed no survival benefit for a maximized EOR (GTR/near GTR: Ref.; PR: HR 1.45 [95% CI, 0.68-3.09]; p = 0.33). Therapy response predictive value of MGMT promoter methylation was evident for RTK I (HR 0.37 [95% CI, 0.19-0.71]; p < 0.01) and RTK II (HR 0.56 [95% CI, 0.34-0.91]; p = 0.02) but not the MES subclass (HR 0.52 [95% CI, 0.27-1.02]; p = 0.06). For local recurrence (n = 112), re-resection conveyed a progression-to-overall survival (POS) benefit (p < 0.01), which was evident in RTK I (p = 0.03) and RTK II (p < 0.01) tumors, but not in MES tumors (p = 0.33)., Conclusion: We demonstrate a survival benefit from maximized EOR for newly diagnosed and recurrent glioblastomas of the RTK I and RTK II but not the MES subclass. Hence, it needs to be debated whether the MES subclass should be treated with maximal surgical resection, especially when located in eloquent areas and at time of recurrence., (© The Author(s) 2022. 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.)

Purpose: Non-invasive prediction of the tumour of origin giving rise to brain metastases (BMs) using MRI measurements obtained in radiological routine and elucidating the biological basis by matched histopathological analysis., Methods: Preoperative MRI and histological parameters of 95 BM patients (female, 50; mean age 59.6 ± 11.5 years) suffering from different primary tumours were retrospectively analysed. MR features were assessed by region of interest (ROI) measurements of signal intensities on unenhanced T1-, T2-, diffusion-weighted imaging and apparent diffusion coefficient (ADC) normalised to an internal reference ROI. Furthermore, we assessed BM size and oedema as well as cell density, proliferation rate, microvessel density and vessel area as histopathological parameters., Results: Applying recursive partitioning conditional inference trees, only histopathological parameters could stratify the primary tumour entities. We identified two distinct BM growth patterns depending on their proliferative status: Ki67 high BMs were larger (p = 0.02), showed less peritumoural oedema (p = 0.02) and showed a trend towards higher cell density (p = 0.05). Furthermore, Ki67 high BMs were associated with higher DWI signals (p = 0.03) and reduced ADC values (p = 0.004). Vessel density was strongly reduced in Ki67 high BM (p < 0.001). These features differentiated between lung cancer BM entities (p ≤ 0.03 for all features) with SCLCs representing predominantly the Ki67 high group, while NSCLCs rather matching with Ki67 low features., Conclusion: Interpretable and easy to obtain MRI features may not be sufficient to predict directly the primary tumour entity of BM but seem to have the potential to aid differentiating high- and low-proliferative BMs, such as SCLC and NSCLC., (© 2022. The Author(s).)

Purpose: With increasing patient self-empowerment and participation in decision making, we hypothesized that patients with adult-type diffuse gliomas, CNS WHO grade 4 who change sites of treatment differ from patients being entirely treated in one neuro-oncological center., Methods: Prospectively collected data from all diffuse glioma grade 4 patients who underwent treatment in our neuro-oncological center between 2012 and 2018 were retrospectively examined for differences between patients having initially been diagnosed and/or treated elsewhere (External Group) and patients having entirely been treated in our neuro-oncological center (Internal Group). Additionally, a matched-pair analysis was performed to adjust for possible confounders., Results: A total of 616 patients was analyzed. Patients from the External Group (n = 78) were significantly younger, more frequently suffered from IDH-mutant astrocytoma grade 4, had a greater extent of tumor resection, more frequently underwent adjuvant therapy and experienced longer overall survival (all p < 0.001). However, after matching these patients to patients of the Internal Group considering IDH mutations, extent of resection, adjuvant therapy, age and gender, no difference in patients' overall survival was observed anymore., Conclusion: The present study demonstrates that mobile diffuse glioma grade 4 patients stand out from a comprehensive diffuse glioma grade 4 patient cohort due to their favorable prognostic characteristics. However, changing treatment sites did not result in survival benefit over similar patients being entirely taken care of within one neuro-oncological institution. These results underline the importance of treatment and molecular markers in glioma disease for patients' self-empowerment, including changing treatment sites according to patients' needs and wishes., (© 2022. The Author(s).)

Current data show that resilience is an important factor in cancer patients’ well-being. We aim to explore the resilience of patients with lower grade glioma (LGG) and the potentially influencing factors. We performed a cross-sectional assessment of adult patients with LGG who were enrolled in the LoG-Glio registry. By phone interview, we administered the following measures: Resilience Scale (RS-13), distress thermometer, Montreal Cognitive Assessment Test for visually impaired patients (MoCA-Blind), internalized stigmatization by brain tumor (ISBI), Eastern Cooperative Oncological Group performance status (ECOG), patients’ perspective questionnaire (PPQ) and typical clinical parameters. We calculated correlations and multivariate regression models. Of 74 patients who were assessed, 38% of those showed a low level of resilience. Our results revealed significant correlations of resilience with distress (p < 0.001, −0.49), MOCA (p = 0.003, 0.342), ECOG (p < 0.001, −0.602), stigmatization (p < 0.001, −0.558), pain (p < 0.001, −0.524), and occupation (p = 0.007, 0.329). In multivariate analyses, resilience was negatively associated with elevated ECOG (p = 0.020, β = −0.383) and stigmatization levels (p = 0.008, β = −0.350). Occupation showed a tendency towards a significant association with resilience (p = 0.088, β = −0.254). Overall, low resilience affected more than one third of our cohort. Low functional status is a specific risk factor for low resilience. The relevant influence of stigmatization on resilience is a novel finding for patients suffering from a glioma and should be routinely identified and targeted in clinical routine., Competing Interests: The authors declare no conflict of interest.