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Purpose: The development of brain metastases (BM) can significantly increase the psycho-oncological burden in cancer patients, requiring timely intervention. In addition, this aspect may negatively affect the course of the disease and treatment outcome. However, screening for psycho-oncological burden is often overlooked in clinical routine. Therefore, we analyzed the extent of psycho-oncological distress in a patient population with BM receiving neurosurgical resection and identified clinical characteristics associated with a high need for psycho-oncological intervention. Methods: We prospectively screened 353 patients (169 female, 184 male, mean age 61.9 years) scheduled for microsurgical resection of one or more BM. Psycho-oncological screening was performed on the day of admission using the Hornheider screening instrument (HSI) and the distress thermometer (DT). Screening results were correlated with demographic and clinical data. Results: Most patients (73.1%) completed the screening questionnaire. Patients who failed to complete the questionnaire presented more frequently with metachronous BM (74.7% vs. 25.3%, p=0.009), were significantly older (p=0.0018), and had a significantly lower KPS score (p=0.0002). Based on the threshold values of the questionnaires, 59.3% of the patients showed a significant psycho-oncological burden requiring immediate intervention. Univariate analysis demonstrated that synchronous BM (p=0.034), tumors in eloquent areas (p=0.001), lower KPS (p=0.031), female gender (p=0.009), and presurgical aphasia (p=0.042) were significantly associated with high psycho-oncological burden. Multivariate analysis showed synchronous BM (p=0.045), female gender (p=0.005), and lower KPS (p=0.028) as independent factors associated with high psycho-oncological burden. Conclusion: The majority of patients with BM have a high psycho-oncological burden. Female gender, synchronous BM, and lower KPS are independently associated with a need for psycho-oncological intervention. [ABSTRACT FROM AUTHOR]

Simple Summary: Functional MRI has become established in the surgery of brain metastases (BM) as a preoperative diagnostic tool to identify intact eloquent cortex areas. Evidence shows that by allowing surgeons to spare these intraoperatively, patients' postoperative outcome is improved in terms of significantly reduced mortality and morbidity. The influence specifically of BM on the fMRI signal and brain networks has scarcely been investigated, as most studies to date refer only to primary brain tumors or include various tumor entities. Our work examined how BM affect cortical activation and brain networks using task-based fMRI. We found a qualitative attenuation of patients' fMRI signal in the metastasis-affected hemisphere compared to the contralateral hemisphere and alterations in all examined brain networks of the patients compared to healthy controls, and also in the contralateral hemisphere. Thus, our results provide insights into the behavior of BM during fMRI examination and their impact on the integrity of the brain. To date, there are almost no investigations addressing functional connectivity (FC) in patients with brain metastases (BM). In this retrospective study, we investigate the influence of BM on hemodynamic brain signals derived from functional magnetic resonance imaging (fMRI) and FC. Motor-fMRI data of 29 patients with BM and 29 matched healthy controls were analyzed to assess percent signal changes (PSC) in the ROIs motor cortex, premotor cortex, and supplementary motor cortex and FC in the sensorimotor, default mode, and salience networks using Statistical Parametric Mapping (SPM12) and marsbar and CONN toolboxes. In the PSC analysis, an attenuation of the BOLD signal in the metastases-affected hemisphere compared to the contralateral hemisphere was significant only in the supplementary motor cortex during hand movement. In the FC analysis, we found alterations in patients' FC compared to controls in all examined networks, also in the hemisphere contralateral to the metastasis. This indicates a qualitative attenuation of the BOLD signal in the affected hemisphere and also that FC is altered by the presence of BM, similarly to what is known for primary brain tumors. This transformation is not only visible in the infiltrated hemisphere, but also in the contralateral one, suggesting an influence of BM beyond local damage. [ABSTRACT FROM AUTHOR]

Background Malignant isocitrate dehydrogenase wild-type (IDHwt) gliomas impose a high symptomatic and psychological burden. Wide distances from patients' homes to cancer centers may affect the delivery of psycho-oncological care. Here, we investigated, in a large brain tumor center with a rural outreach, the initiation of psycho-oncological care depending on spatial distance and impact of psycho-oncological care on emergency visits. Methods Electronic patient charts, the regional tumor registry, and interviews with the primary care physicians were used to investigate clinical data, psycho-oncological care, and emergency unit visits. Interrelations with socio-demographic, clinical, and treatment aspects were investigated using univariable and multivariable binary logistic regression analysis and the Pearson's Chi-square test. Results Of 491, 229 adult patients of this retrospective cohort fulfilled the inclusion criteria for analysis. During the last three months of their lives, 48.9% received at least one psycho-oncological consultation, and 37.1% visited the emergency unit at least once. The distance from the cancer center did neither affect the initiation of psycho-oncological care nor the rate of emergency unit visits. Receiving psycho-oncological care did not correlate with the frequency of emergency unit visits in the last three months of life. Conclusion We conclude that the distance of IDHwt glioma patients' homes from their cancer center, even in a rural area, does not significantly influence the rate of psycho-oncological care. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 micro-vasculature are relevant guidance signals for NSC tropism toward brain tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: In this comprehensive review, we focused on the neurosurgical treatment as an integrative part of the challenging multidisciplinary management of cerebral metastases, a neuro-oncologic entity, which has been observed to have an increased incidence over the last years. In selected cases, the surgical removal of the space-occupying mass reduces the intracranial pressure, normalizes the metabolic environment, reduces the symptom burden, and allows for the intensification of local and systemic adjuvant treatment. In detail, we discuss the incidence of brain metastases, the role of surgical resection, as well as the evolution of current neurosurgical techniques, the surgical morbidity and mortality of single and multiple lesions, and we enlighten the role of surgery for recurrent tumors. The multidisciplinary management of patients with brain metastases (BM) consists of surgical resection, different radiation treatment modalities, cytotoxic chemotherapy, and targeted molecular treatment. This review presents the current state of neurosurgical technology applied to achieve maximal resection with minimal morbidity as a treatment paradigm in patients with BM. In addition, we discuss the contribution of neurosurgical resection on functional outcome, advanced systemic treatment strategies, and enhanced understanding of the tumor biology. [ABSTRACT FROM AUTHOR]

Simple Summary: In order to clarify whether an early development of brain metastases from non-small cell lung cancer represents a poor prognostic factor for further survival we analyzed 377 patients with brain metastases, treated by radiosurgery or surgery at two German institutions. Our results show that an early appearance of brain metastasis does not influence further survival in a comprehensive treatment setting. Objective: We attempted to analyze whether early presentation with brain metastases (BM) represents a poor prognostic factor in patients with non-small cell lung cancer (NSCLC), which should guide the treatment team towards less intensified therapy. Patients and methods: In a retrospective bi-centric analysis, we identified patients receiving surgical treatment for NSCLC BM. We collected demographic-, tumor-, and treatment-related parameters and analyzed their influence on further survival. Results: We included 377 patients. Development of BM was precocious in 99 (26.3%), synchronous in 152 (40.3%), and metachronous in 126 (33.4%) patients. The groups were comparable in terms of age (p = 0.76) and number of metastases (p = 0.11), and histology (p = 0.1); however, mutational status significantly differed (p = 0.002). The precocious group showed the worst clinical status as assessed by Karnofsky performance score (KPS) upon presentation (p < 0.0001). Resection followed by postoperative radiotherapy was the predominant treatment modality for precocious BM, while in syn- and metachronous BM surgical and radio-surgical treatment was balanced. Overall survival (OS) did not differ between the groups (p = 0.76). A good postoperative clinical status (KPS ≥ 70) and the application of any kind of adjuvant systemic therapy were independent predictive factors for OS. Conclusion: Early BM presentation was not associated with worse OS in NSCLC BM patients. [ABSTRACT FROM AUTHOR]

(1) Background: Gangliogliomas comprise a small number of brain tumors. They usually present as World Health Organization (WHO) grade I, and they delineate on gadolinium-enhanced MRI; the surgical goal is wide radical resection, and the course thereafter is usually benign. Fluorescein sodium (FL) tends to accumulate in areas with altered blood–brain barrier (BBB). Thus far, the results provided by prospective and retrospective studies show that the utilization of this fluorophore may be associated with better visualization and improvement of resection for several tumors of the central nervous system. In this study, we retrospectively studied the effect of fluorescein sodium on visualization and resection of gangliogliomas. (2) Methods: Surgical databases in three neurosurgical departments (Regensburg University Hospital; Besta Institute, Milano, Italy; and Liv Hospital, Istanbul, Turkey), with approval by the local ethics committee, were retrospectively reviewed to find gangliogliomas surgically removed by a fluorescein-guided technique by the aid of a dedicated filter on the surgical microscope from April 2014 to February 2020. Eighteen patients (13 women, 5 men; mean age 22.9 years, range 3 to 78 years) underwent surgical treatment for gangliogliomas during 19 operations. Fluorescein was intravenously injected (5 mg/kg) after general anesthesia induction. Tumors were removed using a microsurgical technique with the YELLOW 560 Filter (YE560) (KINEVO/PENTERO 900, Carl Zeiss Meditec, Oberkochen, Germany). (3) Results: No side effects related to fluorescein occurred. In all tumors, contrast enhancement on preoperative MRI correlated with bright yellow fluorescence during the surgical procedure (17 gangliogliomas WHO grade I, 1 ganglioglioma WHO grade II). Fluorescein was considered helpful by the operating surgeon in distinguishing tumors from viable tissue in all cases (100%). Biopsy was intended in two operations, and subtotal resection was intended in one operation. In all other operations considered preoperatively eligible, gross total resection (GTR) was achieved in 12 out of 16 (75%) instances. (4) Conclusions: The use of FL and YE560 is a readily available method for safe fluorescence-guided tumor resection, possibly visualizing tumor margins intraoperatively similar to contrast enhancement in T1-weighted MRI. Our data suggested a positive effect of fluorescein-guided surgery on intraoperative visualization and extent of resection during resection of gangliogliomas. [ABSTRACT FROM AUTHOR]