Prognosis versus Actual Outcomes in Stereotactic Radiosurgery of Brain Metastases: Reliability of Common Prognostic Parameters and Indices.

This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

Cadaveric study of ergonomics and performance using a robotic exoscope with a head-mounted display in spine surgery.

The conventional microscope has the disadvantage of a potentially unergonomic posture for the surgeon, which can affect performance. Monitor-based exoscopes could provide a more ergonomic posture, as already shown in pre-clinical studies. The aim of this study was to test the usability and comfort of a novel head-mounted display (HMD)-based exoscope on spinal surgical approaches in a simulated OR setting. A total of 21 neurosurgeons naïve to the device were participated in this prospective trial. After a standardized training session with the device, participants were asked to perform a single-level thoracolumbar decompression surgery on human cadavers using the exoscope. Subsequently, all participants completed a comfort and safety questionnaire. For the objective evaluation of the performance, all interventions were videotaped and analyzed. Twelve men and nine women with a mean age of 34 (range: 24-57) were participating in the study. Average time for decompression was 15 min (IqR 9.6; 24.2); three participants (14%) terminated the procedure prematurely. In these dropouts, a significantly higher incidence of back/neck pain (p = 0.002 for back, p = 0.046 for neck pain) as well as an increased frequency of HMD readjustments (p = 0.045) and decreased depth perception (p = 0.03) were documented. Overall, the surgeons' satisfaction with the exoscope was 84% (IqR 75; 100). Using a standardized, pre-interventional training, it is possible for exoscope-naïve surgeons to perform sufficient spinal decompression using the HMD-based exoscope with a high satisfaction. However, inaccurate HMD setup prior to the start of the procedure may lead to discomfort and unsatisfactory results.

Surgical Outcome of Patients With Supratentorial Meningiomas Aged 80 Years or Older-Retrospective International Multicenter Study.

BACKGROUND AND OBJECTIVES: Demographic changes will lead to an increase in old patients, a population with significant risk of postoperative morbidity and mortality, requiring neurosurgery for meningiomas. This multicenter study aims to report neurofunctional status after resection of patients with supratentorial meningioma aged 80 years or older, to identify factors associated with outcome, and to validate a previously proposed decision support tool. METHODS: Neurofunctional status was assessed by the Karnofsky Performance Scale (KPS). Patients were categorized in poor (KPS ≤40), intermediate (KPS 50-70), and good (KPS ≥80) preoperative subgroups. Volumetric analyses of tumor and peritumoral brain edema (PTBE) were performed; volumes were scored as small (<10 cm 3 ), medium (10-50 cm 3 ), and large (>50 cm 3 ). RESULTS: The study population consisted of 262 patients, and the median age at surgery was 83.0 years. The median preoperative KPS was 70; 117 (44.7%) patients were allotted to the good, 113 (43.1%) to the intermediate, and 32 (12.2%) to the poor subgroup. The median tumor and PTBE volumes were 30.2 cm 3 and 27.3 cm 3 ; large PTBE volume correlated with poor preoperative KPS status ( P = .008). The 90-day and 1-year mortality rates were 9.0% and 13.2%, respectively. Within the first postoperative year, 101 (38.5%) patients improved, 87 (33.2%) were unchanged, and 74 (28.2%) were functionally worse (including deaths). Each year increase of age associated with 44% (23%-70%) increased risk of 90-day and 1-year mortality. In total, 111 (42.4%) patients suffered from surgery-associated complications. Maximum tumor diameter ≥5 cm (odds ratio 1.87 [1.12-3.13]) and large tumor volume (odds ratio 2.35 [1.01-5.50]) associated with increased risk of complications. Among patients with poor preoperative status and large PTBE, most (58.3%) benefited from surgery. CONCLUSION: Patients with poor preoperative neurofunctional status and large PTBE most often showed postoperative improvements. The decision support tool may be of help in identifying cases that most likely benefit from surgery.

Tumor Location Impacts the Development of Radiation Necrosis in Benign Intracranial Tumors.

BACKGROUND: Radiation necrosis (RN) is a possible late complication of stereotactic radiosurgery (SRS), but only a few risk factors are known. The aim of this study was to assess tumor location in correlation to the development of radiation necrosis for skull base (SB) and non-skull base tumors. METHODS: All patients treated with radiosurgery for benign neoplasms (2004-2020) were retrospectively evaluated. The clinical, imaging and medication data were obtained and the largest axial tumor diameter was determined using MRI scans in T1-weighted imaging with gadolinium. The diagnosis of RN was established using imaging parameters. Patients with tumors located at the skull base were compared to patients with tumors in non-skull base locations. RESULTS: 205 patients could be included. Overall, 157 tumors (76.6%) were located at the SB and compared to 48 (23.4%) non-SB tumors. Among SB tumors, the most common were vestibular schwannomas (125 cases) and meningiomas (21 cases). In total, 32 (15.6%) patients developed RN after a median of 10 (IqR 5-12) months. Moreover, 62 patients (30.2%) had already undergone at least one surgical resection. In multivariate Cox regression, SB tumors showed a significantly lower risk of radiation necrosis with a Hazard Ratio (HR) of 0.252, p < 0.001, independently of the applied radiation dose. Furthermore, higher radiation doses had a significant impact on the occurrence of RN (HR 1.372, p = 0.002). CONCLUSIONS: The risk for the development of RN for SB tumors appears to be low but should not be underestimated. No difference was found between recurrent tumors and newly diagnosed tumors, which may support the value of radiosurgical treatment for patients with recurrent SB tumors.

Same but different. Incidental and symptomatic lower grade gliomas show differences in molecular features and survival.

PURPOSE: Data on differences in overall survival and molecular characteristics between incidental (iLGG) and symptomatic lower grade Glioma (sLGG) are limited. The aim of this study was to investigate differences between patients with iLGG and sLGG. METHODS: All adult patients with a histologically proven diffuse (WHO°II) or anaplastic (WHO°III) glioma who underwent their first surgery at the authors' institution between 2010 and 2019 were retrospectively included. Tumor volume on pre- and postoperative MRI scans was determined. Clinical and routine neuropathological data were gained from patients' charts. If IDH1, ATRX and EGFR were not routinely assessed, they were re-determined. RESULTS: Out of 161 patients included, 23 (14%) were diagnosed as incidental findings. Main reasons for obtaining MRI were: headache(n = 12), trauma(n = 2), MRI indicated by other departments(n = 7), staging examination for cancer(n = 1), volunteering for MRI sequence testing(n = 1). The asymptomatic patients were significantly younger with a median age of 38 years (IqR28-48) vs. 50 years (IqR38-61), p = 0.011. Incidental LGG showed significantly lower preoperative tumor volumes in T1 CE (p = 0.008), FLAIR (p = 0.038) and DWI (p = 0.028). Incidental LGG demonstrated significantly lower incidence of anaplasia (p = 0.004) and lower expression of MIB-1 (p = 0.008) compared to sLGG. IDH1-mutation was significantly more common in iLGG (p = 0.024). Incidental LGG showed a significantly longer OS (mean 212 vs. 70 months, p = 0.005) and PFS (mean 201 vs. 61 months, p = 0.001) compared to sLGG. CONCLUSION: Our study is the first to depict a significant difference in molecular characteristics between iLGG and sLGG. The findings of this study confirmed and extended the results of previous studies showing a better outcome and more favorable radiological, volumetric and neuropathological features of iLGG.

Impact of GAP-43, Cx43 and actin expression on the outcome and overall survival in diffuse and anaplastic gliomas.

Distant intercellular communication in gliomas is based on the expansion of tumor microtubuli, where actin forms cytoskeleton and GAP-43 mediates the axonal conus growth. We aimed to investigate the impact of GAP-43 and actin expression on overall survival (OS) as well as crucial prognostic factors. FFPE tissue of adult patients with diffuse and anaplastic gliomas, who underwent first surgery in our center between 2010 and 2019, were selected. GAP-43, Cx43 and actin expression was analyzed using immunohistochemistry and semi-quantitatively ranked. 118 patients with a median age of 46 years (IqR: 35-57) were evaluated. 48 (41%) presented with a diffuse glioma and 70 (59%) revealed anaplasia. Tumors with higher expression of GAP-43 (p = 0.024, HR = 1.71/rank) and actin (p < 0.001, HR = 2.28/rank) showed significantly reduced OS. IDH1 wildtype glioma demonstrated significantly more expression of all proteins: GAP-43 (p = 0.009), Cx43 (p = 0.003) and actin (p < 0.001). The same was confirmed for anaplasia (GAP-43 p = 0.028, actin p = 0.029), higher proliferation rate (GAP-43 p = 0.016, actin p = 0.038), contrast-enhancement in MRI (GAP-43 p = 0.023, actin p = 0.037) and age (GAP-43 p = 0.004, actin p < 0.001; Cx43 n.s. in all groups). The intercellular distant communication network in diffuse and anaplastic gliomas formed by actin and GAP-43 is associated with a negative impact on overall survival and with unfavorable prognostic features. Cx43 did not show relevant impact on OS.

The relationship between connexin-43 expression and Ki67 in non-glial central nervous system tumors.

BACKGROUND: Advanced intercellular communication is a known oncogenic factor. In the central nervous system, Connexin-43 (Cx43) forms this junctional networking. Moreover, it correlates with the proliferation rate, and thus behavior, of gliomas. We assessed the expression of Cx43 and its relationship to Ki67 in other common central nervous system tumors. METHODS: The expression of Cx43 and Ki67 were assessed in formalin-fixed paraffin embedded samples of human brain metastases, meningiomas, and neurinomas using immunohistochemistry. Neurinomas and meningiomas were jointly evaluated due to similar non-malignant behavior. RESULTS: A total of 14 metastases of different extracerebral carcinomas, 6 meningiomas, and 10 neurinomas were evaluated. Five (36%) metastases and 5 (31%) meningiomas/neurinomas showed minor expression, whereas 6 (43%) metastases and 2 (13%) meningiomas/neurinomas showed no Cx43 expression at all. In 3 (21%) metastases and 9 (56%) meningiomas/neurinomas, moderate or strong expression of Cx43 was identified. The higher expression of Cx43 in meningiomas and neurinomas directly correlated with Ki67, r = 0.53 (P = 0.034). For metastases no significant correlation was found. Mitotic index in meningiomas/neurinomas correlated with Ki67 expression, r = 0.74 (P < 0.001), but did not show statistically significant correlation with Cx43 expression in these tumors. CONCLUSIONS: The expression of Cx43 as a marker of cell-to-cell networking exposed a significant correlation with the Ki67-defined proliferation index in case of primary central nervous system neuroectodermal neoplasms. However, it does not seem to play a comparable role in metastases with extracerebral origin.

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 quantified in three ways: (1) total number of previously performed glioma surgeries (lifetime experience); (2) number of surgeries performed in the previous five 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 affected 19.7% patients. No correlations of lifetime surgeon experience with OS (P = .693), EOR (P = .693), and surgery-related morbidity (P = .435) were identified. Adjuvant therapy was associated with improved OS (P < .001); patients with surgery-related morbidity were less likely to receive adjuvant treatment (P = .002). In multivariable testing, adjuvant therapy (P < .001; HR = 0.064, 95%CI 0.028-0.144) remained the only significant predictor for improved OS. CONCLUSION: 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 for generating a treatment benefit for this cohort.

Mind the gap-the use of sodium fluoresceine for resection of brain metastases to improve the resection rate.

INTRODUCTION AND PURPOSE: Brain metastases appear to be well resectable due to dissectable tumor margins, but postoperative MRI quite often depicts residual tumor with potential influence on tumor control and overall survival. Therefore, we introduced sodium fluoresceine into the routine workflow for brain metastasis resection. The aim of this study was to evaluate whether the use of fluorescence-guided surgery has an impact on postoperative tumor volume and local recurrence. MATERIAL AND METHODS: We retrospectively included patients who underwent surgical resection for intracranial metastases of systemic cancer between 11/2017 and 05/2021 at our institution. Tumor volumes were assessed pre- and postoperatively on T1-CE MRI. Clinical and epidemiological data as well as follow-up were gathered from our prospective database. RESULTS: Seventy-nine patients (33 male, 46 female) were included in this study. Median preoperative tumor volume amounted to 11.7cm3 and fluoresceine was used in 53 patients (67%). Surgeons reported an estimated gross total resection (GTR) in 95% of the cases, while early postoperative MRI could confirm GTR in 72%. Patients resected using fluoresceine demonstrated significantly lower postoperative residual tumor volumes with a difference of 0.7cm3 (p = 0.044) and lower risk of local tumor recurrence (p = 0.033). The use of fluorescence did not influence the overall survival (OS). Postoperative radiotherapy resulted in a significantly longer OS (p = 0.001). DISCUSSION: While GTR rates may be overrated, the use of intraoperative fluorescence may help neurosurgeons to achieve a more radical resection. Fluoresceine seems to facilitate surgical resection and increase the extent of resection thus reducing the risk for local recurrence.

A Multi-Disciplinary Approach to Diagnosis and Treatment of Radionecrosis in Malignant Gliomas and Cerebral Metastases.

Radiation necrosis represents a potentially devastating complication after radiation therapy in brain tumors. The establishment of the diagnosis and especially the differentiation from progression and pseudoprogression with its therapeutic implications requires interdisciplinary consent and monitoring. Herein, we want to provide an overview of the diagnostic modalities, therapeutic possibilities and an outlook on future developments to tackle this challenging topic. The aim of this report is to provide an overview of the current morphological, functional, metabolic and evolving imaging tools described in the literature in order to (I) identify the best criteria to distinguish radionecrosis from tumor recurrence after the radio-oncological treatment of malignant gliomas and cerebral metastases, (II) analyze the therapeutic possibilities and (III) give an outlook on future developments to tackle this challenging topic. Additionally, we provide the experience of a tertiary tumor center with this important issue in neuro-oncology and provide an institutional pathway dealing with this problem.

Surgeon's comfort: The ergonomics of a robotic exoscope using a head-mounted display.

Introduction: Conventional microscopes have certain limitations in terms of posture and ergonomics. Monitor-based exoscopes could solve this problem and thereby lead to less work-related sick leave for surgeons. Research question: The aim of this study was to assess the ergonomics, usability, and neurosurgeon's comfort of a novel three-dimensional head-mounted display-based exoscope in a standardized setting. Material & Methods: 34 neurosurgeons participated in a workshop on the exoscope, which features a head-mounted display and a head gesture-triggered control panel. After completion of a custom-made 10-step microsurgical exercise, image quality and comfort were assessed using a questionnaire. The participants' posture during the exercise was analyzed using a video motion analysis software. Results: 34 participants (median neurosurgical experience: 6 years) were included. The median time to complete the exercise was 12 â€‹min [IqR 9.4, 15.0]. Younger participants (p â€‹= â€‹0.005) and those with video game experience (p â€‹= â€‹0.03) had a significantly steeper learning curve. The median overall satisfaction was at 80% in general and 82% for image quality. The median upper body as well as the median head coronal displacement from the neutral axis were 0°. Participants with less microsurgical experience showed less head/body displacement during the exercise (p â€‹= â€‹0.01). Discussion and conclusion: Using the microsurgical training tool, we were able to depict a steep learning curve with a sufficient learnability of the most relevant commands. The exoscope excelled in usability, image quality as well as in ergonomic and favorable posture and could thus become an alternative to conventional microscopes due to the potentially elevated surgeons' comfort.

The Routine Application of Tumor-Treating Fields in the Treatment of Glioblastoma WHO° IV.

Introduction: Tumor-treating fields (TTFs) are a specific local oncological treatment modality in glioblastoma multiforme WHO° IV (GBM). Their mechanism of action is based on the effect of electrical fields interfering with the mitotic activity of malignant cells. Prospective studies have demonstrated efficacy, but TTF benefits are still controversially discussed. This treatment was implemented in our center as the standard of care in January 2016. We thus discuss the current state of the art and our long-term experience in the routine application of TTF. Methods: The data of 48 patients suffering from GBM and treated with TTF were assessed and compared with previously published studies. Up-to-date information from open sources was evaluated. Results: A total of 31 males and 17 females harboring a GBM were treated with TTF, between January 2016 and August 2021, in our center. In 98% of cases, TTFs were started within 6 weeks after concomitant radiochemotherapy (Stupp protocol). Mean overall survival was 22.6 months (95% CI: 17.3-27.9). Current indications, benefits, and restrictions were evaluated. Future TTF opportunities and ongoing studies were reviewed. Conclusion: TTFs are a feasible and routinely applicable specific oncological treatment option for glioblastoma multiforme WHO° IV. Further research is ongoing to extend the indications and the efficacy of TTF.

The Clinical Frailty Scale as useful tool in patients with brain metastases.

PURPOSE: The Clinical Frailty Scale (CFS) evaluates patients' level of frailty on a scale from 1 to 9 and is commonly used in geriatric medicine, intensive care and orthopedics. The aim of our study was to reveal whether the CFS allows a reliable prediction of overall survival (OS) in patients after surgical treatment of brain metastases (BM) compared to the Karnofsky Performance Score (KPS). METHODS: Patients operated for BM were included. CFS and KPS were retrospectively assessed pre- and postoperatively and at follow-up 3-6 months after resection. RESULTS: 205 patients with a follow-up of 22.8 months (95% CI 18.4-27.1) were evaluated. CFS showed a median of 3 ("managing well"; IqR 2-4) at all 3 assessment-points. Median KPS was 80 preoperatively (IqR 80-90) and 90 postoperatively (IqR 80-100) as well as at follow-up after 3-6 months. CFS correlated with KPS both preoperatively (r = - 0.92; p < 0.001), postoperatively (r = - 0.85; p < 0.001) and at follow-up (r = - 0.93; p < 0.001). The CFS predicted the expected reduction of OS more reliably than the KPS at all 3 assessments. A one-point increase (worsening) of the preoperative CFS translated into a 30% additional hazard to decease (HR 1.30, 95% CI 1.15-1.46; p < 0.001). A one-point increase in postoperative and at follow-up CFS represents a 39% (HR 1.39, 95% CI 1.25-1.54; p < 0.001) and of 42% risk (HR 1.42, 95% CI 1.27-1.59; p < 0.001). CONCLUSION: The CFS is a feasible, simple and reliable scoring system in patients undergoing resection of brain metastasis. The CFS 3-6 months after surgery specifies the expected OS more accurately than the KPS.

The diagnostic value of contrast enhancement on MRI in diffuse and anaplastic gliomas.

PURPOSE: We evaluated differentiations in gadolinium contrast enhancement (CE) between low-grade WHO °II and high-grade WHO °III gliomas in conventional MRI, which have been repeatedly questioned. METHODS: Ninety-nine patients, who underwent first resection of WHO°II and °III gliomas, were retrospectively retrieved from a prospective database. The quantitative metric volume of Gd-CE in T1-weighted pre-operative MRI was measured using volumetric segmentation. RESULTS: The OR to detect CE in anaplastic gliomas was seven times higher than that in diffuse gliomas (CI95% 2.8-17.2, p<0.0001). No CE was seen in 50% (8/16) of focal anaplastic and in 28% (10/36) of entirely anaplastic gliomas. CE was present in 21% (10/47) of diffuse gliomas. Anaplasia correlated with a larger CE volume (r=0.49, p<0.0001) and provided additional 4 cm3 of CE volume compared to entirely diffuse tumors. The OR to have CE was 3.6 times for IDH1 wild-type tumors (CI95% 1.3-10.2, p=0.05) and 4.8 for tumors with ATRX expression (CI95% 1.3-17.2, p=0.05). In all sub-groups, at least a quarter of cases showed no CE at all and there were cases with present CE. CONCLUSION: CE is associated with higher odds of unfavorable prognostic features like anaplasia, wild-type IDH1 and retained ATRX. There was no CE in one-fourth of anaplastic gliomas and half of gliomas with focal anaplasia.

Risk Factors for Radiation Necrosis in Patients Undergoing Cranial Stereotactic Radiosurgery.

PURPOSE: single-staged stereotactic radiosurgery (SRS) is an established part of the multimodal treatment in neuro-oncology. Radiation necrosis after high-dose irradiation is a known complication, but there is a lack of evidence about the risk factors. The aim of this study was to evaluate possible risk factors for radiation necrosis in patients undergoing radiosurgery. METHODS: patients treated with radiosurgery between January 2004 and November 2020 were retrospectively analyzed. The clinical data, imaging and medication were gathered from electronic patient records. The largest diameter of the tumors was measured using MRI scans in T1 weighted imaging with gadolinium and the edema in T2 weighted sequences. The diagnosis of a radiation necrosis was established analyzing imaging criteria combined with clinical course or pathologically confirmed by subsequent surgical intervention. Patients developing radiation necrosis detected after SRS were compared to patients without evidence of an overshooting irradiation reaction. RESULTS: 388 patients were included retrospectively, 61 (15.7%) of whom developed a radiation necrosis. Median follow-up was 24 (6-62) months with a radiation necrosis after 8 (6-12) months. The most frequent tumors were metastases in 47.2% of the cases, followed by acoustic neuromas in 32.2% and meningiomas in 13.4%. Seventy-three (18.9%) patients already underwent one or more previous radiosurgical procedures for different lesions. The mean largest diameter of the tumors amounted to 16.3 mm (±6.1 mm). The median-80%-isodose administered was 16 (14-25) Gy. Of the radiation necroses, 25 (43.1%) required treatment, in 23 (39.7%) thereof, medical treatment was applied and in 2 (3.4%) cases, debulking surgery was performed. In this study, significantly more radiation necroses arose in patients with higher doses (HR 1.3 [CI 1.2; 1.5], p < 0.001) leading to a risk increment of over 180% between a radiation isodose of 14 and 20 Gy. The maximum diameter was a second significant risk factor (p = 0.028) with an HR of 1065 for every 1 mm increase in multivariate analysis. CONCLUSION: large diameter and high doses were reliable independent risk factors leading to more frequent radiation necroses, regardless of tumor type in patients undergoing radiosurgery. Alternative therapeutic procedures may be considered in lesions with large volume and an expected high radiation doses due to the increased risk of developing radiation necrosis.

Age is associated with unfavorable neuropathological and radiological features and poor outcome in patients with WHO grade 2 and 3 gliomas.

With the rising life expectancy and availability of neuroimaging, increased number of older patients will present with diffuse and anaplastic gliomas. The aim of our study was therefore to investigate age-related prognostic clinical, neuropathological and radiological features of lower-grade gliomas. All consecutive patients with diffuse or anaplastic glioma WHO grade 2 and 3 who underwent first tumor resection between 2010 and 2018, were selected from the institutional neuro-oncological database and evaluated. The mean age of 55 males and 44 females was 46 years (SD ± 16). Wild-type IDH1 (p = 0.012), persistent nuclear ATRX expression (p = 0.012) and anaplasia (p < 0.001) were significantly associated with higher age. The CE volume before resection was found to be increased in older patients (r = 0.42, p < 0.0001), and CE rate was higher in the IDH wild-type population only (p = 0.02). The extent of resection did not differ with age. Overall, one year of life resulted in a PFS reduction of 9 days (p = 0.047); in IDH sub-group analysis, this dependency was confirmed only in wild-type tumors (p = 0.05). OS was significantly reduced in older patients (p = 0.033). In conclusion, behavior and prognosis of WHO grade 2 and 3 glioma were unfavorable in correlation to patient's age, even if the extent of resection was comparable. Older age imparted a poorer PFS and higher CE rate only in the IDH wild-type population.

The advanced development of Cx43 and GAP-43 mediated intercellular networking in IDH1 wildtype diffuse and anaplastic gliomas with lower mitotic rate.

PURPOSE: The biologic behavior and the therapeutic resistance of diffuse and anaplastic gliomas varies greatly. This may be explained by differences in cell-to-cell communication, determined by the Cx43-associated junctional activity and the microtubules-defined network, in which GAP-43 is the dominant structural component. We assessed the expression of these crucial communication proteins in samples of patients harboring WHO°II and III gliomas, graded according to the current 4th revised WHO classification. METHODS: Tissue of adult patients with WHO°II and III gliomas, who underwent surgery between 2014 and 2018, were selected from our institutional biobank. GAP-43 and Cx43 expression was analyzed using IHC. Routine clinical and neuropathological findings were additionally retrieved from our institutional prospective database. RESULTS: 43 (57%) males and 33 (43%) females with a median age of 47 (IqR: 35-61) years were selected. IDH1 wildtype tumors showed a significantly higher expression of Cx43 (p = 0.014) and a tendency for increased GAP-43 production. Advanced Cx43 expression significantly correlated with lower mitosis rate (p = 0.014): more in IDH1 wildtype (r = - 0.57, p = 0.003) than in mutated gliomas (r = - 0.37, p = 0.019). There was no difference in Cx43 or GAP-43 expression in relation to anaplastic phenotype, Gadolinum-contrasted enhancement (CE) on MRI and advanced EGFR or p53 expression. CONCLUSIONS: Intercellular communication tends to be more relevant in slower proliferating, e.g. lower malignant tumors. They could have more time to establish this network, providing longitudinally acquired resistance against specific oncological therapy. This feature matches the unfavorable IDH1 wildtype status of glioma and supports the noted malignant behavior of these tumors in the upcoming 5th WHO classification of gliomas.

Effect of the COVID-19 Pandemic on Patient Presentation and Perception to a Neurosurgical Outpatient Clinic.

BACKGROUND: The world currently faces the novel COVID-19 pandemic, with cutbacks in patient care. Little is known about the effects of a pandemic on the presentation and admission to an outpatient clinic. Our aim was to gain a better understanding of the effects of reduced neurosurgical care access from the patient perspective, especially in terms of anxiety and urgency of treatment, and to improve outpatient management in case of a potential second wave and potential restrictions on health care. METHODS: We performed a questionnaire study over a period of 4 weeks following the COVID-19 lockdown at our academic neurosurgical department. A 15-item questionnaire was distributed to the patients with 3 additional questions to be answered by the treating neurosurgeon. RESULTS: A total of 437 questionnaires were analyzed. Overall anxiety to visit a general practitioner or the outpatient facility within the hospital was very low among patients. A quarter of all appointments had to be postponed due to COVID-19, in 0.6% postponement was perceived as incorrect by the treating neurosurgeon. We noted that 43% did not get an appointment due to the restrictions, 20% did not want to bother the medical system, and only 4% were afraid to get infected in the hospital. CONCLUSIONS: Despite COVID-19, patients in need of neurosurgical service were hardly afraid to visit doctors and/or hospitals. Nonetheless, because legal requirements, access has been restricted, causing potential collateral damage in a small subset of neurosurgical patients.