Age, preoperative tumor volume and widening of the internal acoustic meatus are independent factors associated with poor preoperative hearing in vestibular schwannoma patients - results of a single-center retrospective analysis.

Preoperative hearing function shows wide variations among patients diagnosed with vestibular schwannoma. Besides the preoperative tumor size there are other factors that influence the preoperative hearing function that are frequently discussed. A comprehensive analysis of a large cohort of vestibular schwannomas has the potential to describe new insights and influence the preoperative management. We analyzed clinical factors, imaging data and the expression of the proliferation marker MIB1 as potential influencing factors on the preoperative hearing function in a retrospective cohort of 523 primary sporadic vestibular schwannomas. The results of the preoperative audiometry were quantified using the Gardner-Robertson Score. Uni- and multivariate analyses were performed. Serviceable hearing (Gardner-Robertson class 1 or 2) was documented in 391 patients (74.8%). Factors associated with non-serviceable hearing (Gardner-Robertson class 3-5) were patients of older age (p < 0.0001), larger preoperative tumor volume (p = 0.0013) and widening of the internal acoustic meatus compared to the healthy side (p = 0.0353). Gender and differences in the expression of the proliferation marker MIB1 had no influence on preoperative hearing. In the multivariate nominal logistic regression older age (OR 27.60 (CI 9.17-87.18), p < 0.0001), larger preoperative tumor volume (OR 20.20 (CI 3.43-128.58), p = 0.0011) and widening of the internal acoustic canal (OR 7.86 (CI 1.77-35.46), p = 0.0079) remained independent factors associated with non-serviceable hearing. Widening of the internal acoustic canal is an independent factor for non-serviceable preoperative hearing in vestibular schwannoma patients together with older age and larger preoperative tumor volume.

Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas.

Homozygous deletion of CDKN2A/B was recently incorporated into the World Health Organization classification for grade 3 meningiomas. While this marker is overall rare in meningiomas, its relationship to other CDKN2A alterations on a transcriptomic, epigenomic, and copy number level has not yet been determined. We therefore utilized multidimensional molecular data of 1577 meningioma samples from 6 independent cohorts enriched for clinically aggressive meningiomas to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Homozygous CDKN2A/B deletions were identified in only 7.1% of cases but were associated with significantly poorer outcomes compared to tumors without these deletions. Heterozygous CDKN2A/B deletions were identified in 2.6% of cases and had similarly poor outcomes as those with homozygous deletions. Among tumors with intact CDKN2A/B (without a homozygous or heterozygous deletion), we found a distinct difference in outcome based on mRNA expression of CDKN2A, with meningiomas that had elevated mRNA expression (CDKN2Ahigh) having a significantly shorter time to recurrence. The expression of CDKN2A was independently prognostic after accounting for copy number loss and consistently increased with WHO grade and more aggressive molecular and methylation groups irrespective of cohort. Despite the discordant and mutually exclusive status of the CDKN2A gene in these groups, both CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycle pathways but at different checkpoints. High mRNA expression of CDKN2A was also associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. p16 immunohistochemistry could not reliably differentiate between meningiomas with and without CDKN2A deletions but appeared to correlate better with mRNA expression. These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications.

Differences in the expression of SSTR1-5 in meningiomas and its therapeutic potential.

Beyond microsurgical resection and radiation therapy, there are currently no established treatment alternatives for meningioma patients. In selected cases, peptide radio receptor therapy (PRRT) can be implemented. For this purpose, a radionuclide is bound to a substance targeting specific receptors in meningiomas. One of them is somatostatin receptor 2, which can be found in most meningiomas. However, other somatostatin receptors (SSTR) exist, but their expressions have only been described in small case series. In this study, we analyzed the expression of SSTR1, 2A, 3, 4, and 5 in a large cohort of meningiomas in order to enable further refinement of this innovative treatment option. Overall, 726 tumor samples were processed into tissue microarrays and stained for SSTR1, 2A, 3, 4, and 5 immunohistochemically. Microscopic evaluation was done with an established semiquantitative score regarding percentual quantification and staining intensity, and results were correlated with clinical data. There was a significant lower rate of SSTR1 expression in meningiomas of male patients. Older age was associated with higher expression of SSTR1, 2A, and 5 and lower scores for SSTR3 and 4. Tumors treated with radiotherapy before resection showed lower rates of SSTR1 and 5 expression, while recurrent meningiomas had lower SSTR1 scores. Tumor tissue from patients suffering from neurofibromatosis type 2 had lower expression scores for SSTR1, 2, and 5. For SSTR3 and 4, NF2 patients showed higher scores than sporadic tumors. Spinal meningiomas had higher scores for SSTR1, 4, and 5 compared tumor location of the skull base and convexity/falx. Overall, higher WHO grade was associated with lower SSTR scores. While all SSTRs were expressed, there are marked differences of SSTR expression between meningioma subgroups. This has the potential to drive the development of more selective PRRT substances with higher treatment efficacy.

The immunohistochemical expression of SSTR2A is an independent prognostic factor in meningioma.

The expression of somatostatin receptors in meningioma is well established. First, suggestions of a prognostic impact of SSTRs in meningioma have been made. However, the knowledge is based on few investigations in small cohorts. We recently analyzed the expression of all five known SSTRs in a large cohort of over 700 meningiomas and demonstrated significant correlations with WHO tumor grade and other clinical characteristics. We therefore expanded our dataset and additionally collected information about radiographic tumor recurrence and progression as well as clinically relevant factors (gender, age, extent of resection, WHO grade, tumor location, adjuvant radiotherapy, neurofibromatosis type 2, primary/recurrent tumor) for a comprehensive prognostic multivariate analysis (n = 666). The immunohistochemical expression scores of SSTR1, 2A, 3, 4, and 5 were scored using an intensity distribution score ranging from 0 to 12. For recurrence-free progression analysis, a cutoff at an intensity distribution score of 6 was used. Univariate analysis demonstrated a higher rate of tumor recurrence for increased expression scores for SSTR2A, SSTR3, and SSTR4 (p = 0.0312, p = 0.0351, and p = 0.0390, respectively), while high expression levels of SSTR1 showed less frequent tumor recurrences (p = 0.0012). In the Kaplan-Meier analysis, a higher intensity distribution score showed a favorable prognosis for SSTR1 (p = 0.0158) and an unfavorable prognosis for SSTR2A (0.0143). The negative prognostic impact of higher SSTR2A expression remained a significant factor in the multivariate analysis (RR 1.69, p = 0.0060). We conclude that the expression of SSTR2A has an independent prognostic value regarding meningioma recurrence.

Increased proliferation is associated with CNS invasion in meningiomas.

INTRODUCTION: Meningiomas are the most common benign intracranial neoplasms. CNS invasion in meningiomas has been integrated into the 2016 WHO classification of CNS tumors as a stand-alone criterion for atypia. Since then, its prognostic impact has been debated based on contradictory results from retrospective analyses. The aim of the study was to elucidate whether histopathological evidence of CNS invasion is associated with increased proliferative potential. METHODS: We have conducted a quantified measurement of the proliferation marker Ki67 and analyzed its association with CNS invasion determined by histology together with other established prognostic markers of progression. Routine, immunohistochemical staining for Ki67 were digitalized and automatic quantification was done using Image J software. RESULTS: Overall, 1718 meningiomas were assessed. Histopathological CNS invasion was seen in 108 cases (6.7%). Uni- and multivariate analysis revealed a significantly higher Ki67 proliferation rate in meningiomas with CNS invasion (p < 0.0001 and p = 0.0098, respectively). CONCLUSIONS: Meningiomas with histopathological CNS invasion show a higher proliferative activity.

Neuro-oncological patients' and caregivers' psychosocial burden during the COVID-19 pandemic-A prospective study with qualitative content analysis.

OBJECTIVE: The COVID-19 pandemic may reinforce psychosocial distress of neuro-oncological patients. We aimed to (1) differentiate the burden caused by the pandemic versus the tumor and (2) establish topics relevant for brain tumor patients (BTPs) and caregivers. METHODS: Patients and caregivers were prospectively assessed from April 2020-July 2020 by a 10-item comprising interview over the phone, including qualitative and quantitative questions. They were quantitatively evaluated i.a. by the distress thermometer (DT, score 1-10). The qualitative questions were analyzed using structured content analysis: The interview questions defined the main categories. Subcategories were derived by an inductive approach assessing the frequency of patients' and caregivers' answers. RESULTS: A total of 69 patients and 20 caregivers were interviewed; n = 36 were female (49%), mean age was 53 years (range 32-81). Patients' disease-related DT scores were higher than the COVID-19-related DT scores: the median of the disease-related DT score was 7 (range 2-10) versus median of COVID-19-related distress: 5.0 (range 2-7). Caregivers perceived a higher burden due to the disease (DT median disease: 8; range 2-10 vs. DT pandemic: 3, range 0-10). A total of five main and 21 subcategories were elaborated, most frequently mentioned were "restrictions in public and private affairs" (28%), "changes in the psychological well-being" (23%), "limited social interaction by contact restriction" (25%). Subcategories relevant for caregivers were similar to those of BTPs. CONCLUSION: A considerable proportion of patients and caregivers still perceived the brain tumor disease as more burdensome than the pandemic. We established main and subcategories of interview items possibly of great relevance to patients during these difficult times, which could be implemented in the content-related adaption of the psychosocial assessment.

Prognostic value of tumour volume in patients with a poor Karnofsky performance status scale - a bicentric retrospective study.

BACKROUND: Median overall survival (OS) after diagnosis of glioblastoma (GBM) remains 15 months amongst patients receiving aggressive surgical resection, chemotherapy and irradiation. Treatment of patients with a poor preoperative Karnofsky Performance Status Scale (KPSS) is still controversial. Therefore, we retrospectively assessed the outcome after surgical treatment in patients with a KPSS of ≤60%. METHODS: We retrospectively included patients with a de-novo glioblastoma WHO °IV and preoperative KPSS ≤60%, who underwent surgery at two neurosurgical centres between September 2006 and March 2016. We recorded pre- and postoperative tumour volume, pre- and postoperative KPSS, OS, age and MGMT promoter status. RESULTS: One hundred twenty-three patients (58 females/65 males, mean age 67.4 ± 13.4 years) met the inclusion criteria. Seventy-five of the 123 patients (61%) underwent surgical resection. 48/123 patients (39%) received a biopsy. The median preoperative and postoperative tumour volume of all patients was 33.0 ± 31.3 cm3 (IR 15.0-56.5cm3) and 3.1 ± 23.8 cm3 (IR 0.2-15.0 cm3), respectively. The median KPSS was 60% (range 20-60%) preoperatively and 50% (range 0-80%) postoperatively. Patients who received a biopsy showed a median OS for patients who received a biopsy only was 3.0 months (95% CI 2.0-4.0 months), compared to patients who had a resection and had a median OS of 8 months (95% CI 3.1-12.9 months). Age (p < 0.001, HR: 1.045 [95% CI 1.022-1.068]), postoperative tumour volume (p = 0.02, HR: 1.016 [95% CI 1.002-1.029]) and MGMT promotor status (p = 0.016, HR: 0.473 [95% CI 0.257-0.871]) were statistically significant in multivariate analysis. In subgroup analyses only age was shown as a significant prognostic factor in multivariate analyses for patients receiving surgery (p < 0.001, HR: 1.046 [95% CI 1.022-1.072]). In the biopsy group no significant prognostic factors were shown in multivariate analysis. CONCLUSION: GBM patients with a preoperative KPSS of ≤60% might profit from surgical reduction of tumour burden.

The role of Simpson grading in meningiomas after integration of the updated WHO classification and adjuvant radiotherapy.

Since the introduction of the Simpson grading for the extent of resection in meningiomas in 1957, its usefulness in modern neurosurgery has been challenged. Especially, the updated WHO classification regarding brain invasion and the efficacy of radiation therapy has not been taken into account when evaluating the prognostic role of the Simpson grading in this era. We analyzed the clinical and histopathological data of 1571 meningiomas that were surgically resected in the authors' institution between July 2003 and March 2017. Operative reports were reviewed regarding the extent of resection according to Simpson grading. Meningioma subtype according to the updated WHO classification of 2016 and clinical characteristics and time to tumor progression were analyzed. The mean follow-up was 38.4 months (range 1.2 to 195.6). A higher rate of tumor recurrence was observed for male gender, younger age, recurrent tumors, non-spinal tumor localization, higher WHO, and Simpson grades in the univariate analysis. In the multivariate analysis older age, recurrent tumors and higher WHO grades remained negative prognostic factors. Among the different Simpson grades, the relative risk for recurrence was highest for grade IV compared to all other grades (each p < 0.0001), while there was no difference between Simpson grades I and II. Adjuvant radiotherapy showed lower rates of tumor recurrence. Subtotal microsurgical resection remains an independent prognostic factor with a higher rate of tumor recurrence. The prognostic benefit of radical treatment of the dural attachment is questionable and needs to be considered when weighing the intraoperative risks of radicality.

One-on-one mentoring for final year medical students during the neurosurgery rotation.

BACKGROUND: Medical students show varying clinical practical skills when entering their final year clinical clerkship, which is the final period to acquire and improve practical skills prior to their residency. We developed a one-on-one mentoring program to allow individually tailored teaching of clinical practical skills to support final year students with varying skill sets during their neurosurgical clinical clerkship. METHODS: Each participating student (n = 23) was paired with a mentor. At the beginning students were asked about their expectations, teaching preferences and surgical interest. Regular meetings and evaluations of clinical practical skills were scheduled every 2 weeks together with fixed rotations that could be individually adjusted. The one-on-one meetings and evaluations with the mentor gave each student the chance for individually tailored teaching. After completion of the program each student evaluated their experience. RESULTS: The mentoring program was well received by participating students and acquisition or improvement of clinical practical skills was achieved by most students. A varying practical skill level and interest in the field of surgery was seen. CONCLUSIONS: A neurosurgical one-on-one mentoring program is well received by final year medical students and allows for individually tailored learning of clinical practical skills.

Prolonged Temozolomide Maintenance Therapy in Newly Diagnosed Glioblastoma.

BACKGROUND: The impact of prolonging temozolomide (TMZ) maintenance beyond six cycles in newly diagnosed glioblastoma (GBM) remains a topic of discussion. We investigated the effects of prolonged TMZ maintenance on progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: In this retrospective single-center cohort study, we included patients with GBM who were treated with radiation therapy with concomitant and adjuvant TMZ. For analysis, patients were considered who either completed six TMZ maintenance cycles (group B), continued with TMZ therapy beyond six cycles (group C), or stopped TMZ maintenance therapy within the first six cycles (group A). Patients with progression during the first six TMZ maintenance cycles were excluded. RESULTS: Clinical data from 107 patients were included for Kaplan-Meier analyses and 102 for Cox regressions. Median PFS times were 8.1 months (95% confidence interval [CI] 6.1-12.4) in group A, 13.7 months (95% CI 10.6-17.5) in group B, and 20.9 months (95% CI 15.2-43.5) in group C. At first progression, response rates of TMZ/lomustine rechallenge were 47% in group B and 13% in group C. Median OS times were 12.7 months (95% CI 10.3-16.8) in group A, 25.2 months (95% CI 17.7-55.5) in group B, and 28.6 months (95% CI 24.4-open) in group C. Nevertheless, multivariate Cox regression for patients in group C compared with group B that accounted for imbalances of other risk factors showed no different relative risk (RR) for OS (RR 0.77, p = .46). CONCLUSION: Our data do not support a general extension of TMZ maintenance therapy beyond six cycles. The Oncologist 2017;22:570-575 IMPLICATIONS FOR PRACTICE: Radiation therapy with concomitant and adjuvant temozolomide (TMZ) maintenance therapy is still the standard of care in patients below the age of 65 years in newly diagnosed glioblastoma. However, in clinical practice, many centers continue TMZ maintenance therapy beyond six cycles. The impact of this continuation is controversial and has not yet been addressed in prospective randomized clinical trials. We compared the effect of more than six cycles of TMZ in comparison with exactly six cycles on overall survival (OS) and progression-free survival (PFS) by multivariate analysis and found a benefit in PFS but not OS. Thus, our data do not suggest prolonging TMZ maintenance therapy beyond six cycles, which should be considered in neurooncological practice.

Predictors of preoperative and early postoperative seizures in patients with intra-axial primary and metastatic brain tumors: A retrospective observational single center study.

OBJECTIVE: Antiepileptic treatment of brain tumor patients mainly depends on the individual physician's choice rather than on well-defined predictive factors. We investigated the predictive value of defined clinical parameters to formulate a model of risk estimations for subpopulations of brain tumor patients. METHODS: We enclosed 650 patients > 18 years of age who underwent brain tumor surgery and included a number of clinical data. Logistic regressions were performed to determine the effect sizes of seizure-related risk factors and to develop prognostic scores for the occurrence of preoperative and early postoperative seizures. RESULTS: A total of 492 patients (334 gliomas) were eligible for logistic regression for preoperative seizures, and 338 patients for early postoperative seizures. Age ≤ 60 years (odds ratio [OR] = 1.66, p = 0.020), grades I and II glioma (OR = 4.00, p = 0.0002), total tumor/edema volume ≤ 64cm(3) (OR = 2.18, p = 0.0003), and frontal location (OR = 2.28, p = 0.034) demonstrated an increased risk for preoperative seizures. Isocitrate-dehydrogenase mutations (OR = 2.52, p = 0.026) were an independent risk factor in the glioma subgroup. Age ≥ 60 years (OR = 3.32, p = 0.041), total tumor/edema volume ≤ 64cm(3) (OR = 3.17, p = 0.034), complete resection (OR = 15.50, p = 0.0009), diencephalic location (OR = 12.2, p = 0.013), and high-grade tumors (OR = 5.67, p = 0.013) were significant risk factors for surgery-related seizures. Antiepileptics (OR = 1.20, p = 0.60) did not affect seizure occurrence. For seizure occurrence, patients could be stratified into 3 prognostic preoperative and into 2 prognostic early postoperative groups. INTERPRETATION: Based on the developed prognostic scores, seizure prophylaxis should be considered in high-risk patients and patient stratification for prospective studies may be feasible in the future.

Comparative analysis of intraoperative and imaging features of invasive growth in pituitary adenomas.

BACKGROUND: Most pituitary adenomas (PAs), also termed pituitary neuroendocrine tumors, are benign in nature and can be treated effectively by surgical resection, medical treatment, and in special cases by radiotherapy. However, invasive growth can be an important feature of a more aggressive behavior and adverse prognosis. The extension of PAs into the cavernous sinus can be categorized according to the Knosp criteria on magnetic resonance imaging (MRI). Comparative analyses of MRI features and intraoperative findings of invasive growth regarding different clinical factors are still scarce. MATERIALS AND METHODS: We performed a retrospective single-center analysis of 764 PAs that were surgically treated between October 2004 and April 2018. Invasive growth was assessed according to the surgical reports and preoperative MRI (Knosp criteria). Clinical data, such as patient age at diagnosis and gender, histopathological adenoma type, and extent of resection, were collected. RESULTS: Invasive features on MRI were seen in 24.4% (Knosp grades 3A-4, 186/764) of the cases. Intraoperatively, invasion was present in 42.4% (324/764). Complete resection was achieved in 80.0% of adenomas and subtotal resection, in 20.1%. By multivariate analysis, invasion according to intraoperative findings was associated with the sparsely granulated corticotroph (SGCA, P = .0026) and sparsely granulated somatotroph (SGSA, P = .0103) adenoma type as well as age (P = .0287). Radiographic invasion according to Knosp grades 3A-4 correlated with age (P = .0098), SGCAs (P = .0005), SGSAs (P = .0351), and gonadotroph adenomas (P = .0478). Both criteria of invasion correlated with subtotal resection (P = .0001, respectively). CONCLUSIONS: Both intraoperative and radiographic signs of invasive growth are high-risk lesions for incomplete extent of resection and occur more frequently in older patients. A particularly high prevalence of invasion can be found in the SGCA and SGSA types. Cavernous sinus invasion is also more common in gonadotroph adenomas. Usage of the Knosp classification is a valuable preoperative estimation tool.

Preoperative growth dynamics of untreated glioblastoma: Description of an exponential growth type, correlating factors, and association with postoperative survival.

Background: Little is known about the growth dynamics of untreated glioblastoma and its possible influence on postoperative survival. Our aim was to analyze a possible association of preoperative growth dynamics with postoperative survival. Methods: We performed a retrospective analysis of all adult patients surgically treated for newly diagnosed glioblastoma at our center between 2010 and 2020. By volumetric analysis of data of patients with availability of ≥3 preoperative sequential MRI, a growth pattern was aimed to be identified. Main inclusion criterion for further analysis was the availability of two preoperative MRI scans with a slice thickness of 1 mm, at least 7 days apart. Individual growth rates were calculated. Association with overall survival (OS) was examined by multivariable. Results: Out of 749 patients screened, 13 had ≥3 preoperative MRI, 70 had 2 MRI and met the inclusion criteria. A curve estimation regression model showed the best fit for exponential tumor growth. Median tumor volume doubling time (VDT) was 31 days, median specific growth rate (SGR) was 2.2% growth per day. SGR showed negative correlation with tumor size (rho = -0.59, P < .001). Growth rates were dichotomized according to the median SGR.OS was significantly longer in the group with slow growth (log-rank: P = .010). Slower preoperative growth was independently associated with longer overall survival in a multivariable Cox regression model for patients after tumor resection. Conclusions: Especially small lesions suggestive of glioblastoma showed exponential tumor growth with variable growth rates and a median VDT of 31 days. SGR was significantly associated with OS in patients with tumor resection in our sample.

The prognostic role of the immunohistochemical expression of S100 in meningiomas.

BACKGROUND: Despite best clinical management, meningioma patients experience tumor recurrence. Efforts have been made to improve the prognostic stratification of meningiomas. Recently, a multi-faceted molecular classification suggested that the marker S100 is associated with a favorable outcome, making a further analysis in a larger cohort interesting. MATERIALS AND METHODS: The immunohistochemical staining for S100 was analyzed in 1669 paraffin-embedded meningioma samples. The distribution and association with clinical data and progression-free survival via radiographic tumor recurrence were assessed. RESULTS: Of 1669 cases, 218 tumors showed strong S100 expression (13.1%). A significantly higher frequency of S100 positive meningiomas was observed in meningiomas of female patients, tumors with spinal and convexity/falx location, primary tumor surgery, NF2, higher extent of resection, lower WHO CNS grade, adjuvant radiotherapy and recurrence-free tumors during follow-up. Univariate analysis revealed a favorable progression-free survival for meningiomas with S100 expression (p = 0.0059) but not in the multivariate analysis. Higher S100 frequency was independently associated with female gender (p = 0.0003), NF2 (p < 0.0001), tumor location (p < 0.0001) and lower WHO CNS grade (p = 0.0133). CONCLUSIONS: The positive prognostic impact of S100 is mostly attributed to the confounding clinical factors gender, tumor location, NF2 status and WHO CNS grade.

Potential of pre-operative MRI features in glioblastoma to predict for molecular stem cell subtype and patient overall survival.

AIM OF THE STUDY: A molecular signature based on 10 mRNA abundances that characterizes the mesenchymal-to-proneural phenotype of glioblastoma stem(like) cells (GSCs) enriched in primary culture has been previously established. As this phenotype has been proposed to be prognostic for disease outcome the present study aims to identify features of the preoperative MR imaging that may predict the GSC phenotype of individual tumors. MATERIAL/METHODS: Molecular mesenchymal-to-proneural mRNA signatures and intrinsic radioresistance (SF4, survival fraction at 4 Gy) of primary GSC-enriched cultures were associated with survival data and pre-operative MR imaging of the corresponding glioblastoma patients of a prospective cohort (n = 24). The analyzed imaging parameters comprised linear vectors derived from tumor volume, necrotic volume and edema as contoured manually. RESULTS: A necrosis/tumor vector ratio and to a weaker extent the product of this ratio and the edema vector were identified to correlate with the mesenchymal-to-proneural mRNA signature and the SF4 of the patient-derived GSC cultures. Importantly, both parameter combinations were predictive for overall survival of the whole patient cohort. Moreover, the combination of necrosis/tumor vector ratio and edema vector differed significantly between uni- and multifocally recurring tumors. CONCLUSION: Features of the preoperative MR images may reflect the molecular signature of the GSC population and might be used in the future as a prognostic factor and for treatment stratification especially in the MGMT promotor-unmethylated sub-cohort of glioblastoma patients.

Correction: Gonçalves et al. Macrophage and Lymphocyte Infiltration Is Associated with Volumetric Tumor Size but Not with Volumetric Growth in the Tübingen Schwannoma Cohort. Cancers 2021, 13, 466.

The authors would like to make a correction to their published paper [...].

Differences in intraoperative sampling during meningioma surgery regarding CNS invasion - Results of a survey on behalf of the EANS skull base section.

Introduction: and Research Question: Invasive growth of meningiomas into CNS tissue is rare but of prognostic significance. While it has entered the WHO classification as a stand-alone criterion for atypia, its true prognostic impact remains controversial. Retrospective analyses, on which the current evidence is based, show conflicting results. Discordant findings might be explained by different intraoperative sampling methodologies. Material and methods: To assess the applied sampling methods in the light of the novel prognostic impact of CNS invasion, an anonymous survey was designed and distributed via the EANS website and newsletter. The survey was open from June 5th until July 15th, 2022. Results: After exclusion of 13 incomplete responses, 142 (91.6%) datasets were used for statistical analysis. Only 47.2% of participants' institutions utilize a standardized sampling method, and 54.9% pursue a complete sampling of the area of contact between the meningioma surface and CNS tissue. Most respondents (77.5%) did not change their sampling practice after introduction of the new grading criteria to the WHO classification of 2016. Intraoperative suspicion of CNS invasion changes the sampling for half of the participants (49.3%). Additional sampling of suspicious areas of interest is reported in 53.5%. Dural attachment and adjacent bone are more readily sampled separately if tumor invasion is suspected (72.5% and 74.6%, respectively), compared to meningioma tissue with signs of CNS invasion (59.9%). Discussion and conclusions: Intraoperative sampling methods during meningioma resection vary among neurosurgical departments. There is need for a structured sampling to optimize the diagnostic yield of CNS invasion.