The Role of Fibroblast Activation Protein in Glioblastoma and Gliosarcoma: A Comparison of Tissue, 68Ga-FAPI-46 PET Data, and Survival Data.

Despite their unique histologic features, gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast activation protein (FAP) is a component of a tumor-specific subpopulation of fibroblasts that plays a critical role in tumor growth and invasion. Some case studies suggest an elevated expression of FAP in glioblastoma and a particularly strong expression in gliosarcoma attributed to traits of predominant mesenchymal differentiation. However, the prognostic impact of FAP and its diagnostic and therapeutic potential remain unclear. Here, we investigate the clinical relevance of FAP expression in gliosarcoma and glioblastoma and how it correlates with 68Ga-FAP inhibitor (FAPI)-46 PET uptake. Methods: Patients diagnosed with gliosarcoma or glioblastoma without sarcomatous differentiation with an overall survival of less than 2.5 y were enrolled. Histologic examination included immunohistochemistry and semiquantitative scoring of FAP (0-3, with higher values indicating stronger expression). Additionally, 68Ga-FAPI-46 PET scans were performed in a subset of glioblastomas without sarcomatous differentiation patients. The clinical SUVs were correlated with FAP expression levels in surgically derived tumor tissue and relevant prognostic factors. Results: Of the 61 patients who were enrolled, 13 of them had gliosarcoma. Immunohistochemistry revealed significantly more FAP in gliosarcomas than in glioblastomas without sarcomatous differentiation of tumor tissue (P < 0.0001). In the latter, FAP expression was confined to the perivascular space, whereas neoplastic cells additionally expressed FAP in gliosarcoma. A significant correlation of immunohistochemical FAP with SUVmean and SUVpeak of 68Ga-FAPI-46 PET indicates that clinical tracer uptake represents FAP expression of the tumor. Although gliosarcomas express higher levels of FAP than do glioblastomas without sarcomatous differentiation, overall survival does not significantly differ between the groups. Conclusion: The analysis reveals a significant correlation between SUVmean and SUVpeak in 68Ga-FAPI-46 PET and immunohistochemical FAP expression. This study indicates that FAP expression is much more abundant in the gliosarcoma subgroup of glioblastomas. This could open not only a diagnostic but also a therapeutic gap, since FAP could be explored as a theranostic target to enhance survival in a distinct subgroup of high-risk brain tumor patients with poor survival prognosis.

Preoperative cervical traction with Gardner-Wells tongs: who profits most?

BACKGROUND: Preoperative traction with the Gardner-Wells tongs (PTGWT) is a valuable option for cervical spine injuries with malalignment. The aim of this study was to analyze the factors related to the treatment success of PTGWT. METHODS: All consecutive cases with PTGWT due to cervical spine injury with malalignment treated between 01/2010 and 09/2020 were included. Patients' records were reviewed for demographic and clinical characteristics. Treatment success was evaluated upon the angle correction in the sagittal plane using the computed tomography scans before and after the treatment. RESULTS: Of 20 patients in the final analysis (median age: 77.5 years; 12 females [60%]), 14 individuals were treated for the type-II odontoid fracture, and six cases presented with subluxation fractures between C3 and C7. After PTGWT and subsequent intraoperative reposition, there was an improvement of the median deviation angle from initial 32° to 5.5°. PTGWT resulted in a significant improvement of the median deviation angle for the odontoid (17°, P<0.0001), but not for the subluxation (4°, P=0.10) fractures. The time interval between trauma and PTGWT was associated with the treatment success of subluxation (P=0.051) but not of odontoid (P=0.87) fractures. Older individuals aged ≥51 years showed better reposition results with PTGWT (17° vs. 7.5°, P=0.02). There were no PTGWT-related complications in the cohort. CONCLUSIONS: PTGWT is an effective and safe treatment for cervical spine injuries with malalignment. The patients with odontoid fractures might particularly profit from the PTGWT. Treatment delay seems more relevant for PTGWT success in subluxation than in odontoid fractures.

Precision neuro-oncology: a pilot analysis of personalized treatment in recurrent glioma.

PURPOSE: When brain cancer relapses, treatment options are scarce. The use of molecularly matched targeted therapies may provide a feasible and efficacious way to treat individual patients based on the molecular tumor profile. Since little information is available on this strategy in neuro-oncology, we retrospectively analyzed the clinical course of 41 patients who underwent advanced molecular testing at disease relapse. METHODS: We performed Sanger sequencing, targeted next generation sequencing, and immunohistochemistry for analysis of potential targets, including programmed death ligand 1, cyclin D1, phosphorylated mechanistic target of rapamycin, telomerase reverse transcriptase promoter mutation, cyclin-dependent kinase inhibitor 2A/B deletion, or BRAF-V600E mutation. In selected patients, whole exome sequencing was conducted. RESULTS: The investigation included 41 patients, of whom 32 had isocitrate dehydrogenase (IDH) wildtype glioblastoma. Molecular analysis revealed actionable targets in 31 of 41 tested patients and 18 patients were treated accordingly (matched therapy group). Twenty-three patients received molecularly unmatched empiric treatment (unmatched therapy group). In both groups, 16 patients were diagnosed with recurrent IDH wildtype glioblastoma. The number of severe adverse events was comparable between the therapy groups. Regarding the IDH wildtype glioblastoma patients, median progression-free survival (mPFS) and median overall survival (mOS) were longer in the matched therapy group (mPFS: 3.8 versus 2.0 months, p = 0.0057; mOS: 13.0 versus 4.3 months, p = 0.0357). CONCLUSION: These encouraging data provide a rationale for molecularly matched targeted therapy in glioma patients. For further validation, future study designs need to additionally consider the prevalence and persistence of actionable molecular alterations in patient tissue.

Long-term outcome after management of pilocytic astrocytoma in the posterior fossa in a pediatric population.

Background and purpose: To assess the impact of posterior fossa pilocytic astrocytoma (PA) removal in pediatric patients, with special focus on postoperative neurological outcome after repeated surgery for tumor remnants. Methods: Our institutional database was screened for patients with PA treated between 2000 and 2019. Patients ≤ 18 years of age with complete clinical records, preoperative contrast enhanced magnetic resonance imaging (MRI) and postoperative follow-up time of ≥ 6 months were suitable for study inclusion. Functional outcome was quantified with the modified Ranking Scale (mRS) score and assessed at admission, at discharge and at every follow-up investigation. Predictors of hydrocephalus, cranial nerve deficits and tumor recurrence were evaluated. Results: A total of 57 pediatric patients with a mean age of 7.7 ± 4.8 years were included in the analysis. 27 (47.3%) children suffered from hydrocephalus at diagnosis, out of which 19 (33.3%) required a subsequent VP-Shunt. 22 (39.3%) patients had a partial resection, of which 9 (40.9%) went through second-look surgery. 2 patients with initially radiological confirmation of complete resection, had a tumor recurrence at FU and needed second-look surgery. Among the children requiring second-look surgery, 7 (63.6%) had a complete resection. Favorable outcome (mRS≤2) after initial and second-look surgery was observed in 52 patients (91.2%). Univariate analysis identified tumor location in the floor of the 4th ventricle (p = 0.030), and repeated surgery for tumor remnant removal (p = 0.043) as predictors for post-operative cranial nerve deficits. Multivariate analysis confirmed this independent association. The incidence of tumor recurrence occurred more often in patients with previous partial resection (p = 0.009) as well as in lesions located in the cerebellar peduncles (p = 0.043). Partial resection remained an independent predictor after multivariate logistic regression analysis (p = 0.045). Conclusions: Incomplete resection of posterior fossa PA is a risk factor for tumor recurrence and repeated surgery to remove tumor remnants increases the risk of new postoperative deficits. Thus, the risk of iatrogenic deterioration due to second look surgery should be implemented in the primary pre- and intraoperative decision-making.

CT and DSA for evaluation of spontaneous intracerebral lobar bleedings.

Purpose: This study retrospectively examined the extent to which computed tomography angiography (CTA) and digital subtraction angiography (DSA) can help identify the cause of lobar intracerebral bleeding. Materials and methods: In the period from 2002 to 2020, data from patients who were >18 years at a university and an academic teaching hospital with lobar intracerebral bleeding were evaluated retrospectively. The CTA DSA data were reviewed separately by two neuroradiologists, and differences in opinion were resolved by consensus after discussion. A positive finding was defined as an underlying vascular etiology of lobar bleeding. Results: The data of 412 patients were retrospectively investigated. DSA detected a macrovascular cause of bleeding in 125/412 patients (33%). In total, sixty patients had AVMs (15%), 30 patients with aneurysms (7%), 12 patients with vasculitis (3%), and 23 patients with dural fistulas (6%). The sensitivity, specificity, positive and negative predictive values, and accuracy of CTA compared with DSA were 93, 97, 100, and 97%. There were false-negative CTA readings for two AVMs and one dural fistula. Conclusion: The DSA is still the gold standard diagnostic modality for detecting macrovascular causes of ICH; however, most patients with lobar ICH can be investigated first with CTA, and the cause of bleeding can be found. Our results showed higher sensitivity and specificity than those of other CTA studies.

Time interval between the diagnosis of breast cancer and brain metastases impacts prognosis after metastasis surgery.

PURPOSE: Breast cancer (BC) is the most frequently diagnosed tumor entity in women. Occurring at different time intervals (TI) after BC diagnosis, brain metastases (BM) are associated with poor prognosis. We aimed to identify the risk factors related to and the clinical impact of timing on overall survival (OS) after BM surgery. METHODS: We included 93 female patients who underwent BC BM surgery in our institution (2008-2019). Various clinical, radiographic, and histopathologic markers were analyzed with respect to TI and OS. RESULTS: The median TI was 45.0 months (range: 9-334.0 months). Fifteen individuals (16.1%) showed late occurrence of BM (TI ≥ 10 years), which was independently related to invasive lobular BC [adjusted odds ratio (aOR) 9.49, 95% confidence interval (CI) 1.47-61.39, p = 0.018] and adjuvant breast radiation (aOR 0.12, 95% CI 0.02-0.67, p = 0.016). Shorter TI (< 5 years, aOR 4.28, 95% CI 1.46-12.53, p = 0.008) was independently associated with postoperative survival and independently associated with the Union for International Cancer Control stage (UICC) III-IV of BC (aOR 4.82, 95% CI 1.10-21.17, p = 0.037), midline brain shift in preoperative imaging (aOR10.35, 95% CI 1.09-98.33, p = 0.042) and identic estrogen receptor status in BM (aOR 4.56, 95% CI 1.35-15.40, p = 0.015). CONCLUSIONS: Several factors seem to influence the period between BC and BM. Occurrence of BM within five years is independently associated with poorer prognosis after BM surgery. Patients with invasive lobular BC and without adjuvant breast radiation are more likely to develop BM after a long progression-free survival necessitating more prolonged cancer aftercare of these individuals.

Prediction of Short and Long Survival after Surgery for Breast Cancer Brain Metastases.

Background: Brain metastases requiring surgical treatment determine the prognosis of patients with breast cancer. We aimed to develop the scores for the prediction of short (<6 months) and long (≥3 years) survival after BCBM surgery. Methods: Female patients with BCBM surgery between 2008 and 2019 were included. The new scores were constructed upon independent predictors for short and long postoperative survival. Results: In the final cohort (n = 95), 18 (18.9%) and 22 (23.2%) patients experienced short and long postoperative survival, respectively. Breast-preserving surgery, presence of multiple brain metastases and age ≥ 65 years at breast cancer diagnosis were identified as independent predictors of short postoperative survival. In turn, positive HER2 receptor status in brain metastases, time interval ≥ 3 years between breast cancer and brain metastases diagnosis and KPS ≥ 90% independently predicted long survival. The appropriate short and long survival scores showed higher diagnostic accuracy for the prediction of short (AUC = 0.773) and long (AUC = 0.775) survival than the breast Graded Prognostic Assessment score (AUC = 0.498/0.615). A cumulative survival score (total score) showed significant association with overall survival (p = 0.001). Conclusion: We identified predictors independently impacting the prognosis after BCBM surgery. After external validation, the presented scores might become useful tools for the selection of proper candidates for BCBM surgery.

A New Subform? Fast-Progressing, Severe Neurological Deterioration Caused by Spinal Epidural Lipomatosis.

Spinal epidural lipomatosis (SEL) is a rare condition caused by hypertrophic growth of epidural fat. The prevalence of SEL in the Western world is approximately 1 in 40 patients and is likely to increase due to current medical and socio-economic developments. Rarely, SEL can lead to rapid severe neurological deterioration. The pathophysiology, optimal treatment, and outcome of these patients remain unclear. This study aims to widen current knowledge about this "SEL subform" and to improve its clinical management. A systematic literature review according to the PRISMA guidelines using PubMed, Scopus, Web of Science, and Cochrane Library was used to identify publications before 7 November 2021 reporting on acute/rapidly progressing, severe SEL. The final analysis comprised 12 patients with acute, severe SEL. The majority of the patients were male (9/12) and multimorbid (10/12). SEL mainly affected the thoracic part of the spinal cord (11/12), extending a median number of 7 spinal levels (range: 4-19). Surgery was the only chosen therapy (11/12), except for one critically ill patient. Regarding the outcome, half of the patients regained independence (6/11; = modified McCormick Scale ≤ II). Acute, severe SEL is a rare condition, mainly affecting multimorbid patients. The prognosis is poor in nearly 50% of the patients, even with maximum therapy. Further research is needed to stratify patients for conservative or surgical treatment.

Radiographic markers of breast cancer brain metastases: relation to clinical characteristics and postoperative outcome.

OBJECTIVE: Occurrence of brain metastases BM is associated with poor prognosis in patients with breast cancer (BC). Magnetic resonance imaging (MRI) is the standard of care in the diagnosis of BM and determines further treatment strategy. The aim of the present study was to evaluate the association between the radiographic markers of BCBM on MRI with other patients' characteristics and overall survival (OS). METHODS: We included 88 female patients who underwent BCBM surgery in our institution from 2008 to 2019. Data on demographic, clinical, and histopathological characteristics of the patients and postoperative survival were collected from the electronic health records. Radiographic features of BM were assessed upon the preoperative MRI. Univariable and multivariable analyses were performed. RESULTS: The median OS was 17 months. Of all evaluated radiographic markers of BCBM, only the presence of necrosis was independently associated with OS (14.5 vs 22.5 months, p = 0.027). In turn, intra-tumoral necrosis was more often in individuals with shorter time interval between BC and BM diagnosis (< 3 years, p = 0.035) and preoperative leukocytosis (p = 0.022). Moreover, dural affection of BM was more common in individuals with positive human epidermal growth factor receptor 2 status (p = 0.015) and supratentorial BM location (p = 0.024). CONCLUSION: Intra-tumoral necrosis demonstrated significant association with OS after BM surgery in patients with BC. The radiographic pattern of BM on the preoperative MRI depends on certain tumor and clinical characteristics of patients.

Fully Automated MR Based Virtual Biopsy of Cerebral Gliomas.

OBJECTIVE: The aim of this study was to investigate the diagnostic accuracy of a radiomics analysis based on a fully automated segmentation and a simplified and robust MR imaging protocol to provide a comprehensive analysis of the genetic profile and grading of cerebral gliomas for everyday clinical use. METHODS: MRI examinations of 217 therapy-naïve patients with cerebral gliomas, each comprising a non-contrast T1-weighted, FLAIR and contrast-enhanced T1-weighted sequence, were included in the study. In addition, clinical and laboratory parameters were incorporated into the analysis. The BraTS 2019 pretrained DeepMedic network was used for automated segmentation. The segmentations generated by DeepMedic were evaluated with 200 manual segmentations with a DICE score of 0.8082 ± 0.1321. Subsequently, the radiomics signatures were utilized to predict the genetic profile of ATRX, IDH1/2, MGMT and 1p19q co-deletion, as well as differentiating low-grade glioma from high-grade glioma. RESULTS: The network provided an AUC (validation/test) for the differentiation between low-grade gliomas vs. high-grade gliomas of 0.981 ± 0.015/0.885 ± 0.02. The best results were achieved for the prediction of the ATRX expression loss with AUCs of 0.979 ± 0.028/0.923 ± 0.045, followed by 0.929 ± 0.042/0.861 ± 0.023 for the prediction of IDH1/2. The prediction of 1p19q and MGMT achieved moderate results, with AUCs of 0.999 ± 0.005/0.711 ± 0.128 for 1p19q and 0.854 ± 0.046/0.742 ± 0.050 for MGMT. CONCLUSION: This fully automated approach utilizing simplified MR protocols to predict the genetic profile and grading of cerebral gliomas provides an easy and efficient method for non-invasive tumor decoding.

Electrolyte and renal disorders in patients with newly diagnosed glioblastoma.

Purpose: Disturbances of electrolytes and renal function have been linked to the prognosis of critically ill patients and recently also of cancer patients. This study aimed to assess electrolyte and renal disorders in glioblastoma patients and evaluate their prognostic effect. Methods: Medical records of patients with newly diagnosed glioblastoma between 2005 and 2018 were retrospectively reviewed for electrolyte and renal function parameters and for demographic, clinical and outcome parameters. Results: Electrolyte and renal function disorders were associated with poorer survival in univariate and Kaplan-Meier analysis. Multivariate analysis revealed hypochloremia as an independent prognostic factor for overall and 1-year survival. Conclusion: Only hypochloremia showed an association with glioblastoma prognosis, independent of other known prognostic factors, as age or molecular status.

PaCO2-management in the neuro-critical care of patients with subarachnoid hemorrhage.

The partial pressure of carbon dioxide (PaCO2) in the arterial blood is a strong vasomodulator affecting cerebral blood flow and the risk of cerebral edema and ischemia after acute brain injury. In turn, both complications are related to poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to analyze the effect of PaCO2 levels on the course and outcome of aSAH. All patients of a single institution treated for aSAH over 13.5 years were included (n = 633). Daily PaCO2 values from arterial blood gas measurements were recorded for up to 2 weeks after ictus. The study endpoints were: delayed cerebral ischemia (DCI), need for decompressive craniectomy due to increased intracranial pressure > 20 mmHg refractory to conservative treatment and poor outcome at 6-months follow-up (modified Rankin scale > 2). By correlations with the study endpoints, clinically relevant cutoffs for the 14-days mean values for the lowest and highest daily PaCO2 levels were defined by receiver operating characteristic curve analysis. Association with the study endpoints for the identifies subgroups was analyzed using multivariate analysis. The optimal range for PaCO2 values was identified between 30 and 38 mmHg. ASAH patients with poor initial condition (WFNS 4/5) were less likely to show PaCO2 values within the range of 30-38 mmHg (p < 0.001, OR = 0.44). In the multivariate analysis, PaCO2 values between 30 and 38 mmHg were associated with a lower risk for decompressive craniectomy (p = 0.042, aOR = 0.27), DCI occurrence (p = 0.035; aOR = 0.50), and poor patient outcome (p = 0.004; aOR = 0.42). The data from this study shows an independent positive association between low normal mean PaCO2 values during the acute phase of aSAH and patients' outcome. This effect might be attributed to the reduction of intracranial hypertension and alterations in the cerebral blood flow.

Risk score for outcome prediction after microsurgical resection of spinal ependymoma (SOURSE score).

OBJECTIVE: Microsurgical resection of spinal ependymomas is associated with a considerable risk of postoperative neurological deterioration. We aimed to develop a risk score for outcome prediction after surgery for spinal ependymoma. MATERIALS AND METHODS: All patients who underwent microsurgical resection of spinal ependymoma between 1980 and 2015 were included. Different perioperative parameters were collected for the score construction. Poor outcome was defined as the modified McCormick Scale (MMCS) >2 at 6 months after surgery. RESULTS: Of 131 patients (mean age: 45.6 ± 16.7 years; 63 females), 38 cases (29%) showed poor outcome. Based on the univariate analysis, preoperative MMCS, subtotal tumor resection, proximal tumor level on the spinal cord, tumor extension, intramedullary location, and WHO grading were included in the multivariate analysis. The final risk score consisted of the following independent predictors: preoperative MMCS > 1 (1 point), proximal tumor level at Th 10 and higher (1 point), and tumor extension ≥ 3 vertebrae (1 point). The constructed score (0-3 points; Score for OUtcome after Resection of Spinal Ependymoma [SOURSE]) showed high diagnostic accuracy (area under the curve [AUC] = 0.883), which was superior to preoperative MMCS (AUC = 0.798) and Karnofsky Performance Status (AUC = 0.794). Patients scoring 0, 1, 2, and 3 points showed poor outcome in 0%, 12.9%, 54.6%, and 76.2% of the cases respectively. CONCLUSION: The presented SOURSE score based on preoperative neurologic condition, tumor location, and tumor extension could accurately predict the postoperative outcome in patients undergoing microsurgery of spinal ependymoma. Our data should be validated in a prospective trial.

Analysis of Brain Natriuretic Peptide Levels after Traumatic Acute Subdural Hematoma and the Risk of Post-Operative Cerebral Infarction.

Traumatic acute subdural hematoma (aSDH) is associated with a high mortality rate caused by post-operative cerebral infarction. Recently, brain natriuretic peptide (BNP) was considered a reliable biomarker in the acute phase of traumatic brain injuries. We therefore aimed in this study to analyze BNP levels on admission, identify the predictors of their elevation, and assess the relationship between BNP and the risk of post-operative cerebral infarction. Patients with isolated, unilateral, traumatic aSDH who were admitted to our department between July 2017 and May 2020 were enrolled in this study. On admission, cranial computer tomography (CCT) and BNP sampling were simultaneously performed. Additionally, the time between head trauma and BNP sampling (TTS) was assessed. Admission radiographic variables included hematoma volumes, midline shift, and degree of brain edema. Cerebral infarction was detected on postoperative CCT. In total, 130 patients were included in this study. Surgical treatment was performed in 82.3% (n = 107) of cases. The multiple regression analysis showed that larger hematoma volumes (p = 0.032) and advanced age (p = 0.005) were independent predictors of elevated BNP when TTS <24 h. The binomial logistical regression analysis identified BNP with a cutoff value of <29.4 pg/mL (TTS = 3-12 h, adjusted odds ratio [aOR] = 16.5, p = 0.023) as an independent predictor of post-operative cerebral infarction. Elevated BNP levels in the first 24 h post-trauma were related to larger hematoma volumes and advanced age. Further, an increased risk of post-operative cerebral infarction was identified in patients with lower BNP levels in the post-traumatic period 3-12 h.

Role of Brain Natriuretic Peptide in the Prediction of Early Postoperative Seizures Following Surgery for Traumatic Acute Subdural Hematoma: A Prospective Study.

INTRODUCTION: Brain natriuretic peptide (BNP) is a reliable biomarker in the acute phase of traumatic brain injury. However, the relationship between BNP and traumatic acute subdural hematoma (aSDH) has not yet been addressed. This study aimed to analyze BNP levels on admission in surgically treated patients and assess their relationship with early postoperative seizures (EPS) and functional outcomes. METHODS: Patients with unilateral traumatic aSDH who were surgically treated in our department between July 2017 and May 2020 were included in the study. BNP was preoperatively measured. Patients' neurologic condition, radiographic variables on initial cranial computed tomography, sodium serum levels on admission, and occurrence of EPS were prospectively assessed. Functional outcome was assessed using the modified Rankin Scale (mRS) at discharge and follow-up (at 2-3 months). A poor outcome was defined by a mRS score > 3. RESULTS: EPS occurred in 20 (19.6%) of 102 surgically treated patients in the final cohort on the median day 3. A significant association between EPS and a poor Glasgow Coma Scale score at the 7th postoperative day was found, which in turn independently predicted a poor functional outcome at discharge and follow-up. Nonetheless, EPS were not associated with poor functional outcomes. The multivariate analysis revealed BNP > 95.4 pg/ml (aOR = 5.7, p = 0.003), sodium < 137.5 mmol/l (aOR = 4.6, p = 0.009), and left-sided aSDH (aOR = 4.4, p = 0.020) as independent predictors of EPS. CONCLUSION: In the early postoperative phase of traumatic aSDH, EPS were associated with worse neurologic conditions, which in turn independently predicted poor outcomes at discharge and follow-up. Although several EPS risk factors have already been elucidated, this study presents BNP as a novel reliable predictor of EPS. Further larger studies are needed to determine whether a more precise estimate of EPS risk using BNP levels can be reached.

How about Levetiracetam in Glioblastoma? An Institutional Experience and Meta-Analysis.

Despite multimodal treatment, the prognosis of patients with glioblastoma (GBM) remains poor. Previous studies showed conflicting results on the effect of antiepileptic drugs (AED) on GBM survival. We investigated the associations of different AED with overall survival (OS) and progression-free survival (PFS) in a large institutional GBM cohort (n = 872) treated January 2006 and December 2018. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the evidence on the value of AED for GBM prognosis. Of all perioperatively administered AED, only the use of levetiracetam (LEV) was associated with longer OS (median: 12.8 vs. 8.77 months, p < 0.0001) and PFS (7 vs. 4.5 months, p = 0.001). In the multivariable analysis, LEV was independently associated with longer OS (aHR = 0.74, p = 0.017) and PFS (aHR = 0.68, p = 0.008). In the meta-analysis with 5614 patients from the present and seven previously published studies, outcome benefit for OS (HR = 0.83, p = 0.02) and PFS (HR = 0.77, p = 0.02) in GBM individuals with LEV was confirmed. Perioperative treatment with LEV might improve the prognosis of GBM patients. We recommend a prospective randomized controlled trial addressing the efficacy of LEV in GBM treatment.

HER2 Receptor Conversion Is a strong Survival Predictor in Patients with Breast Cancer Brain Metastases.

BACKGROUND: Hormone and human epidermal growth factor receptor 2 (HER2/neu) receptor status is prognostic and predictive in breast cancer (BC) and guides the choice of therapy. However, owing to receptor conversion, the receptor status can differ in metastases compared with that of the primary tumor. The aim of the present study was to analyze the prognostic value of receptor status, receptor conversion, and clinical parameters in patients with resected BC brain metastases (BMs). METHODS: Patients with BCBMs treated at our institution from July 2007 to December 2019 were eligible for the present study. The receptor status of the BC and corresponding BMs and the occurrence of receptor conversion were separately recorded for 3 common receptors: HER2/neu, estrogen receptor, and progesterone receptor. The association between the receptor status or receptor conversion and clinical parameters was adjusted for outcome-relevant patient and tumor characteristics. RESULTS: The final analysis included 78 patients. HER2/neu receptor status in BMs was associated with overall survival (P = 0.033). Receptor conversion was identified in 39 patients (50.0%): HER2/neu, n = 9 (11.5%); estrogen receptor, n = 22 (28.2%); and progesterone receptor, n = 25 (32.1%). In the final multivariate Cox regression analysis, HER2/neu receptor conversion (adjusted hazard ratio [aHR], 3.58; P = 0.006), Karnofsky performance status score <70% (aHR, 3.11; P = 0.048), infratentorial BM location (aHR, 2.49; P = 0.007), and age ≥55 years at BM diagnosis (aHR, 2.20; P = 0.046) were independently associated with poorer survival. CONCLUSIONS: Of the 3 common BC receptors, only HER2/neu receptor conversion was strongly associated with the prognosis of patients with surgically treated BCBMs. The clinical relevance of the reevaluation of receptor status in BMs favors surgical treatment of patients with noneloquent BCBMs.

Case Report: Pseudomeningeosis and Demyelinating Metastasis-Like Lesions From Checkpoint Inhibitor Therapy in Malignant Melanoma.

Immune checkpoint inhibitors (ICIs) have considerably expanded the effective treatment options for malignant melanoma. ICIs revert tumor-associated immunosuppression and potentiate T-cell mediated tumor clearance. Immune-related neurologic adverse events (irNAEs) manifest in the central (CNS) or peripheral nervous system (PNS) and most frequently present as encephalitis or myasthenia gravis respectively. We report on a 47-year old male patient with metastatic melanoma who developed signs of cerebellar disease five weeks after the start of ICI treatment (ipilimumab and nivolumab). Magnetic resonance imaging (MRI) of the brain and spine revealed multiple new contrast enhancements suggestive of parenchymal and leptomeningeal metastasis. Cerebral spinal fluid (CSF) evaluation showed a lymphomononuclear pleocytosis in the absence of tumor cells. Subsequent stereotactic brain biopsy confirmed demyelinating disease. High-dose corticosteroid treatment resulted in immediate improvement of the clinical symptoms. MRI scans and CSF re-evaluation were conducted six weeks later and showed a near-complete remission. The strong resemblance to neoplastic CNS dissemination and irNAEs is a particularly difficult diagnostic challenge. Treating physicians should be aware of irNAEs as those can be effectively treated with high-dose steroids.

The Subarachnoid Hemorrhage-Weather Myth: A Long-Term Big Data and Deep Learning Analysis.

Objective: The frequency of aneurysmal subarachnoid hemorrhage (aSAH) presents complex fluctuations that have been attributed to weather and climate changes in the past. In the present long-term big data and deep learning analysis, we have addressed this long-held myth. Methods: Bleeding dates and basic demographic data for all consecutive patients (n = 1,271) admitted to our vascular center for treatment of aSAH between January 2003 and May 2020 (6,334 days) were collected from our continuously maintained database. The meteorological data of the local weather station, including 13 different weather and climate parameters, were retrieved from Germany's National Meteorological Service for the same period. Six different deep learning models were programmed using the Keras framework and were trained for aSAH event prediction with meteorological data from January 2003 to June 2017, with 10% of this dataset applied for data validation and model improvement. The dataset from July 2017 to May 2020 was tested for aSAH event prediction accuracy for all six models using the area under the receiver operating characteristic curve (AUROC) as the metric. Results: The study group comprised of 422 (33.2%) male and 849 (66.8%) female patients with an average age of 55 ± 14 years. None of the models showed an AUROC larger than 60.2. From the presented data, the influence of weather and climate on the occurrence of aSAH events is extremely unlikely. Conclusion: The myth of special weather conditions influencing the frequency of aSAH is disenchanted by this long-term big data and deep learning analysis.

The 2016 Edition of the WHO Classification of Primary Brain Tumors: Applicable to Assess Individual Risk of Recurrence in Atypical Meningioma? A Single-Center Experience.

BACKGROUND AND STUDY AIMS/OBJECT: Despite the relevance of molecular criteria for brain tumor diagnosis and prognosis, meningioma grading is still solely based on histologic features. Atypical meningiomas (AMs; WHO grade II) display a great histologic heterogeneity and individual courses of disease can differ significantly. This study aimed to identify clinically aggressive AMs that are prone to early recurrence after gross total resection (GTR) by assessing a specific histologic score. PATIENTS AND METHODS: A retrospective analysis of 28 consecutive patients (17 females and 11 males; mean age of 62 years [range: 35-88 years]) treated in our institution between January 2006 and December 2015 was performed. Basic demographic and clinical characteristics were assessed. A scoring scale was designed to address the histologic diversity by summing up the individual histologic features in every tumor sample. According to that, points were awarded as follows: major AM defining criterion (3 points) and minor criterion (1 point). RESULTS: The subclassification based on our specific histologic score revealed no significant difference in frequency of one (46.4%) or two (42.9%) AM defining features; three criteria were less frequently seen (10.7%). Mean follow-up was 61.89 ± 9.03 months. Local recurrence occurred in 35.7% after a mean time of 37.4 ± 22.6 months after primary surgery. Age > 60 years was significantly associated with a shorter progression-free survival (PFS). There was a trend toward shorter PFS with increasing scores, tantamount with the presence of several AM defining histologic criteria in one sample. No tumor relapse was seen when diagnosis was based only on minor criteria. CONCLUSION: AMs display a histologic diversity. There is a trend toward shorter PFS with increasing numbers of AM defining histologic features. The inclusion of this score in the decision algorithm regarding further treatment for patients >60 years after GTR might be helpful and should be evaluated in further studies.