The importance of considering competing risks in recurrence analysis of intracranial meningioma.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

ALA-RDT in GBM: protocol of the phase I/II dose escalation trial of radiodynamic therapy with 5-Aminolevulinic acid in patients with recurrent glioblastoma.

BACKGROUND: Despite improvements in surgical as well as adjuvant therapies over the last decades, the prognosis for patients with glioblastoma remains poor. Five-Aminolevulinic acid (5-ALA) induced porphyrins are already used for fluorescence-guided resection and as photosensitizer for photodynamic therapy. New findings reveal their potential use as sensitizing agents in combination with ionizing radiation. METHODS: We initiated a phase I/II dose escalation study, treating patients with recurrence of glioblastoma with oral 5-ALA concurrent to radiotherapy (RT). This prospective single-center study based in the University Hospital Münster aims to recruit 30 patients over 18 years of age with histologically verified recurrence of supratentorial glioblastoma in good performance status (KPS ≥ 60). Following a 3 + 3 dose-escalation design, patients having undergone re-resection will receive a 36 Gy RT including radiodynamic therapy fractions (RDT). RDT constitutes of oral administration of 5-ALA before the irradiation session. Two cohorts will additionally receive two fractions of neoadjuvant treatment three and two days before surgery. To determine the maximum tolerated dose of repeated 5-ALA-administration, the number of RDT-fractions will increase, starting with one to a maximum of eight fractions, while closely monitoring for safety and toxicity. Follow-up will be performed at two and five months after treatment. Primary endpoint will be the maximum tolerated dose (MTD) of repeated ALA-administration, secondary endpoints are event-free-, progression-free-, and overall-survival. Additionally, 5-ALA metabolites and radiobiological markers will be analysed throughout the course of therapy and tissue effects after neoadjuvant treatment will be determined in resected tissue. This protocol is in accordance with the SPIRIT guidelines for clinical trial protocols. DISCUSSION: This is the protocol of the ALA-RDT in GBM-study, the first-in-man evaluation of repeated administration of 5-ALA as a radiosensitizer for treatment of recurrent glioblastoma. TRIAL REGISTRATION: This study was approved by the local ethics committee of the Medical Association of Westphalia-Lippe and the University of Münster on 12.10.2022, the German federal institute for Drugs and medical devices on 13.10.2022 and the federal office for radiation protection on 29.08.2022. This trial was registered on the public European EudraCT database (EudraCT-No.: 2021-004631-92) and is registered under www.cliniclatrials.gov (Identifier: NCT05590689).

Radiomics-Based Prediction of TERT Promotor Mutations in Intracranial High-Grade Meningiomas.

PURPOSE: In meningiomas, TERT promotor mutations are rare but qualify the diagnosis of anaplasia, directly impacting adjuvant therapy. Effective screening for patients at risk for promotor mutations could enable more targeted molecular analyses and improve diagnosis and treatment. METHODS: Semiautomatic segmentation of intracranial grade 2/3 meningiomas was performed on preoperative magnetic resonance imaging. Discriminatory power to predict TERT promoter mutations was analyzed using a random forest algorithm with an increasing number of radiomic features. Two final models with five and eight features with both fixed and differing radiomics features were developed and adjusted to eliminate random effects and to avoid overfitting. RESULTS: A total of 117 image sets including training (N = 94) and test data (N = 23) were analyzed. To eliminate random effects and demonstrate the robustness of our approach, data partitioning and subsequent model development and testing were repeated a total of 100 times (each time with repartitioned training and independent test data). The established five- and eight-feature models with both fixed and different radiomics features enabled the prediction of TERT with similar but excellent performance. The five-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 91.8%/94.3%, mean accuracy of 85.5%/88.9%, mean sensitivity of 88.6%/91.4%, mean specificity of 83.2%/87.0%, and a mean Cohen's Kappa of 71.0%/77.7%. The eight-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 92.7%/94.6%, mean accuracy of 87.3%/88.9%, mean sensitivity of 89.6%/90.6%, mean specificity of 85.5%/87.5%, and a mean Cohen's Kappa of 74.4%/77.6%. Of note, the addition of further features of up to N = 8 only slightly increased the performance. CONCLUSIONS: Radiomics-based machine learning enables prediction of TERT promotor mutation status in meningiomas with excellent discriminatory performance. Future analyses in larger cohorts should include grade 1 lesions as well as additional molecular alterations.

Which risk factors significantly influence the outcome of traumatic brain injured patients with alcohol use disorder?

PURPOSE: Every year, approximately 10 million people worldwide suffer a traumatic brain injury that leads to hospitalization or mortality. Chronic and acute alcohol intoxication increase the risk of developing traumatic brain injury. Alcohol use disorder (AUD) as a predictor of outcome in neurosurgical patients and the definition of risk factors have been sparsely addressed so far. This study aims to improve the understanding of the effects of alcohol use disorder in the context of neurosurgical therapy. METHODS: This study included patients admitted to Münster University Hospital with a traumatic brain injury and alcohol use disorder from January 1, 2010, to December 31, 2018. Univariate and multivariate analyses were performed to identify risk factors for a poorer outcome, assessed by the Glasgow Outcome Score. RESULTS: Of the 197 patients included, 156 (79%) were male, and 41 (21%) were female, with a median age of 49 years (IQR 38-58 years). In multivariate analyses, age (p < 0.001), the occurrence of a new neurologic deficit (p < 0.001), the development of hydrocephalus (p = 0.005), and CT-graphic midline shift due to intracerebral hemorrhage (p = 0.008) emerged as significant predictors of a worse outcome (GOS 1-3). In addition, the level of blood alcohol concentration correlated significantly with the occurrence of seizures (p = 0.009). CONCLUSIONS: Early identification of risk factors in patients with alcohol use disorder and traumatic brain injury is crucial to improve the outcome. In this regard, the occurrence of hydrocephalus or seizures during the inpatient stay should be considered as cause of neurological deterioration in this patient group.

Prognosis and histology of sporadic synchronous and metachronous meningiomas and comparative analyses with singular lesions.

Synchronous or metachronous growth of multiple tumors (≥ 2) is found in up to 20% of meningioma patients. However, biological as well as histological features and prognosis are largely unexplored. Clinical and histological characteristics were retrospectively investigated in 95 patients harboring 226 multiple meningiomas (MMs) and compared with 135 cases of singular meningiomas (SM) using uni- and multivariate analyses. In MM, tumors occurred synchronously and metachronously in 62% and 38%, respectively. WHO grade was intra-individually constant in all but two MMs, and histological subtype varied in 13% of grade 1 tumors. MM occurred more commonly in convexity/parasagittal locations, while SM were more frequent at the skull base (p < .001). In univariate analyses, gross total resection (p = .014) and high-grade histology in MM were associated with a prolonged time to progression (p < .001). Most clinical characteristics and rates of high-grade histology were similar in both groups (p ≥ .05, each). Multivariate analyses showed synchronous/metachronous meningioma growth (HR 4.50, 95% CI 2.26-8.96; p < .001) as an independent predictor for progression. Compared to SM, risk of progression was similar in cases with two (HR 1.56, 95% CI .76-3.19; p = .224), but exponentially raised in patients with 3-4 (HR 3.25, 1.22-1.62; p = .018) and ≥ 5 tumors (HR 13.80, 4.06-46.96; p < .001). Clinical and histological characteristics and risk factors for progression do not relevantly differ between SM and MM. Although largely constant, histology and WHO grade occasionally intra-individually vary in MM. A distinctly higher risk of disease progression in MM as compared to SM might reflect different underlying molecular alterations.

Postoperative surveillance in cranial and spinal tumor neurosurgery: when is this warranted?

OBJECTIVE: The outbreak of COVID-19 and the sudden increase in the number of patients requiring mechanical ventilation significantly affected the management of neurooncological patients. Hospitals were forced to reallocate already scarce human resources to maximize intensive care unit (ICU) capacities, resulting in a significant postponement of elective procedures for patients with brain and spinal tumors, who traditionally require elective postoperative surveillance on ICU or intermediate care wards. This study aimed to characterize those patients in whom postoperative monitoring is required by analyzing early postoperative complications and associated risk factors. METHODS: All patients included in the analysis experienced benign or malignant cerebral or intradural tumors and underwent surgery between September 2017 and May 2019 at University Hospital Münster, Germany. Patient data were generated from a semiautomatic, prospectively designed database. The occurrence of adverse events within 24 hours and 30 days postoperatively-including unplanned reoperation, postoperative hemorrhage, CSF leakage, and pulmonary embolism-was chosen as the primary outcome measure. Furthermore, reasons and risk factors that led to a prolonged stay on the ICU were investigated. By performing multivariable logistic regression modeling, a risk score for early postoperative adverse events was calculated by assigning points based on beta coefficients. RESULTS: Eight hundred eleven patients were included in the study. Eleven patients (1.4%) had an early adverse event within 24 hours, which was either an unplanned reoperation (0.9%, n = 7) or a pulmonary embolism (0.5%, n = 4) within 24 hours. To predict the incidence of early postoperative complications, a score was developed including the number of secondary diagnoses, BMI, and incision closure time, termed the SOS score. According to this score, 0.3% of the patients were at low risk, 2.5% at intermediate risk, and 12% at high risk (p < 0.001). CONCLUSIONS: Postoperative surveillance in cranial and spinal tumor neurosurgery might only be required in a distinct patient collective. In this study, the authors present a new score allowing efficient prediction of the likelihood of early adverse events in patients undergoing neurooncological procedures, thus helping to stratify the necessity for ICU or intermediate care unit beds. Nevertheless, validation of the score in a multicenter prospective setting is needed.

Pronounced mediastinal emphysema after restorative treatment of the lower left molar-a case report and a systematic review of the literature.

This case report presents an iatrogenic induced mediastinal emphysema after restorative treatment of the lower left second molar, aimed to highlight the potential life-threatening consequences, and providing diagnostics and treatment concepts of complicated dental induced emphysema based on literature review. A 74-year-old female patient was admitted to the emergency department due to a fall on her shoulder. Additional finding was a significant swelling of the face and neck. In the computer tomography of the head, neck, and thorax, a humerus fracture and pronounced soft tissue emphysema from the infraorbital region to the mediastinum was detected. The patient reported that she had been treated by her dentist 4 days earlier. The treatment had to be discontinued after beginning of a pronounced swelling. Other reasons for the emphysema could be excluded out on an interdisciplinary teamwork. The patient was monitored as an inpatient for 5 days and received intravenous antibiotic therapy. This case report shows the rare complication of pronounced mediastinal emphysema after root canal treatment. Emphysema should always be a differential diagnosis of soft tissue swelling and, in case of doubt, a general medical presentation should be made.

Vascular anomalies in patients with growth hormone-secreting pituitary adenomas: illustrative case report and systematic review of the literature.

PURPOSE: Endonasal resection is the first-line treatment for patients harboring growth hormone (GH)-secreting pituitary adenomas. The complexity of the parasellar neurovascular structures makes pre-operative diagnostic imaging essential to understanding the anatomy of this region. We aimed to describe vascular anomalies in acromegalic patients and emphasize their relevance for surgery and preoperative planning. METHODS: A systematic review following the PRISMA statement was performed in July 2021. RESULTS: Thirty-three studies were evaluated. Elevated GH and insulin-like growth factor-1 (IGF-1) levels are linked to the occurrence of cardiovascular risk factors. This is attributed to endothelial dysfunction, mainly caused by changes in flow-mediated dilatation (FMD), which is probably the main cause of vascular anomalies in acromegaly. The occurrence of protrusions of the internal carotid artery (ICA) (35-53%), a narrow intercarotid distance, and an asymmetrical course was described. In 13-18% of acromegalic patients, the presence of an intracerebral aneurysm could be reported (incidence in the general population:0.8-1.3%). The selected studies were however performed with a small patient sample (range:1-257). We present a case report of a 57y/o male patient with anomalies of the ICA ("kissing carotid arteries") harboring a GH-secreting adenoma, which was resected via an endoscopic endonasal approach. CONCLUSIONS: There is an association between acromegaly and endothelial dysfunction, which increases cardiovascular risk factors and vascular anomalies. Preoperative vascular imaging, e.g., CT angiography, should be implemented as a standard to identify patients at risk and estimate surgical morbidity. However, no evidence-based recommendations exist so far, so future studies are necessary.

Expression of decitabine-targeted oncogenes in meningiomas in vivo.

Treatment of meningiomas refractory to surgery and irradiation is challenging and effective chemotherapies are still lacking. Recently, in vitro analyses revealed decitabine (DCT, 5-aza-2'-deoxycytidine) to be effective in high-grade meningiomas and, moreover, to induce hypomethylation of distinct oncogenes only sparsely described in meningiomas in vivo yet.Expression of the corresponding onco- and tumor suppressor genes TRIM58, FAM84B, ELOVL2, MAL2, LMO3, and DIO3 were analyzed and scored by immunohistochemical staining and RT-PCR in samples of 111 meningioma patients. Correlations with clinical and histological variables and prognosis were analyzed in uni- and multivariate analyses.All analyzed oncogenes were highly expressed in meningiomas. Expression scores of TRIM58 tended to be higher in benign than in high-grade tumors 20 vs 16 (p = .002) and all 9 samples lacking TRIM58 expression displayed WHO grade II/III histology. In contrast, median expression scores for both FAM84B (6 vs 4, p ≤ .001) and ELOVL2 (9 vs 6, p < .001) were increased in high-grade as compared to benign meningiomas. DIO3 expression was distinctly higher in all analyzed samples as compared to the reference decitabine-resistant Ben-Men 1 cell line. Increased ELOVL2 expression (score ≥ 8) correlated with tumor relapse in both uni- (HR: 2.42, 95%CI 1.18-4.94; p = .015) and multivariate (HR: 2.09, 95%CI 1.01-4.44; p = .046) analyses.All oncogenes involved in DCT efficacy in vitro are also widely expressed in vivo, and expression is partially associated with histology and prognosis. These results strongly encourage further analyses of DCT efficiency in meningiomas in vitro and in situ.

Changes in hormones of the thyroid axis after tracheostomy and their influence on regeneration in patients with head and neck cancer: A prospective study.

This prospective study aimed to compare and evaluate changes in hormones of the thyroid axis affected by tracheostomy due to surgical treatment in patients with oral cancer. The patients were evaluated with regard to serum levels of the thyroid axis - free T3/triiodothyronine (fT3) and free T4/thyroxine (fT4), as well as thyroid-stimulating hormone (TSH) - at fixed perioperative time points: during the tumor staging about 1 week before operation, immediately before and within 6 h after operation, 2 days after operation, and about 10 days after operation. Additionally, data on the patients' characteristics (age, gender), relevant secondary diagnoses, duration of ventilation in the intensive care unit, and perioperative complications were obtained and analyzed. In total, 51 patients with an average age of 68.29 years (±11.82) were included. Analyses of thyroid hormones directly before and after tracheostomy showed a significant postoperative decrease in circulating TSH (p = 0.005) and fT3 (p < 0.001), whilst a significant increase in fT4 values (p < 0.001) was found. Nine patients showed perioperative complications, such as infection, emphysema, or requiring a revision operation. Eleven patients were diagnosed with a cardiac problem or suffered from agitation after operation. Within the limitations of the study it seems that hormonal changes following tracheostomy in critically ill patients should be monitored and thyroid hormone adjustment should be taken into account because the latter might lead to lower mortality and morbidity during hospitalization in these patients. CLINICAL TRIAL REGISTRATION NUMBER: DRKS00023942.

The applicability of established clinical and histopathological risk factors for tumor recurrence during long-term postoperative care in meningioma patients.

Risk factors to predict late-onset tumor recurrence in meningioma patients are urgently needed to schedule control intervals during long-term follow-up. We therefore analyzed the value of established risk factors for postoperative meningioma recurrence for the prediction of long-term prognosis. Correlations of clinical and histopathological variables with tumor relapse after 3, 5, and 10 years following microsurgery were analyzed in uni- and multivariate analyses, and compared to findings in the entire cohort. In the entire cohort (N = 1218), skull base location (HR: 1.51, 95%CI 1.05-2.16; p = .026), Simpson ≥ IV resections (HR: 2.41, 95%CI 1.52-3.84; p < .001), high-grade histology (HR: 3.70, 95%CI 2.50-5.47; p < .001), and male gender (HR: 1.46, 95%CI 1.01-2.11; p = .042) were independent risk factors for recurrence. Skull base location (HR: 1.92, 95%CI 1.17-3.17; p = .010 and HR: 2.02, 95%CI 1.04-3.95; p = .038) and high-grade histology (HR: 1.87, 95%CI 1.04-3.38; p = .038 and HR: 2.29, 95%CI 1.07-4.01; p = .034) but not subtotal resection (HR: 1.53, 95%CI .68-3.45; p = .303 and HR: 1.75, 95%CI .52-5.96; p = .369) remained correlated with recurrence after a recurrence-free follow-up of ≥ 3 and ≥ 5 years, respectively. Postoperative tumor volume was related with recurrence in general (p < .001) but not beyond a follow-up of ≥ 3 years (p > .05). In 147 patients with a follow-up of ≥ 10 years, ten recurrences occurred and were not correlated with any of the analyzed variables. Skull base tumor location and high-grade histology but not the extent of resection should be considered when scheduling the long-term follow-up after meningioma surgery. Recurrences ≥ 10 years after surgery are rare, and predictors are lacking.

Microbiological Characteristics and Surgical Management of Animal-Bite-Related Oral & Maxillofacial Injuries: A Single Center's Experience.

The objective of the current study is to retrospectively evaluate animal-bite injuries and to gain insight into the epidemiology, accident consequences and treatment concept of these accidents in oral and maxillofacial surgery. Data of patients, who were admitted January 2015 and April 2021, were retrospectively evaluated regarding the patients' characteristics (age, gender), facial distribution of substance defects/partial amputations, duration of hospitalization, operation treatments and antibiotic treatments. Data of 75 patients were included. Patients were bitten by dogs (n = 69.92%), cats (n = 4) and horses (n = 2). Lower eyelid/cheek complex was the most affected region (n = 37, 32.74%). Most of the patients between 0 and 3 years had to be operated on under general anesthesia (p = 0.011), while most of the adults could be operated on under local anesthesia (p = 0.007). In the age group 0-12 years, 30 patients (68%) were operated on under general anesthesia. Ampicillin/Sulbactam (48%) was the antibiotic most used. Antibiotics were adjusted after wound swabs in case of wound infections or critical wound conditions. This means that resistant antibiotics were stopped, and sensitive antibiotics were used. Structured surgical and antibiotic management of animal-bite wounds in the maxillofacial region is the most important factor for medical care to avoid long-term aesthetic consequences. Public health actions and policies under the leadership of an interdisciplinary committee could improve primary wound management, healing outcome and information status in the general population.

Predicting postoperative seizure development in meningiomas - Analyses of clinical, histological and radiological risk factors.

INTRODUCTION: Seizures after meningioma surgery are common, with a distinct impact on postoperative life quality. Sufficient risk factors for seizure development are sparsely known but needed to improve perioperative patient counseling and, eventually, antiepileptic treatment. MATERIALS AND METHODS: Correlations between clinical, radiological and histological variables and the onset of new seizures following surgery for initially diagnosed cranial meningioma were retrospectively analyzed in uni- and multivariate analyses. RESULTS: 752 preoperatively seizure-naïve patients (569 females, 76 % and 183 males, 24 %) with a median age of 57 years were included. Postoperative seizures occurred in 69 cases (9 %). In univariate analyses, seizures were correlated with preoperative Karnofsky Score < 80 (OR: 1.91, 95 % CI 1.01-3.59; p = .045), convexity/parasagittal tumor location (OR: 1.77, 95 % CI 1.06-2.95; p = .030), heterogenous contrast-enhancement of the tumor (OR: 2.24, 95 % CI 1.14-4.39; p = .019) and intratumoral calcifications (OR: 3.35, 95 % CI 1.59-7.05; p = .001). Multivariable analyses revealed age at the time of surgery (OR: 1.04, 95 % CI 1.01-1.07; p = .009) and intratumoral calcifications on preoperative imaging (OR: 3.70, 95 % CI 1.73-7.92; p = .001) as risk factors for postoperative seizures. Based on multivariate analyses, a score for discrimination of patients at low (3 %), intermediate (11 %) and high risk (17 %) of postoperative seizures (AUC: 0.7, p < .001) was conducted. In subgroup analyses, postoperative hemorrhage (OR: 2.90, 95 % CI 1.13-7.46; p = .028) and hydrocephalus (OR: 3.65, 95 % CI 1.48-9.01; p = .005) were correlated with postoperative seizures. CONCLUSION: Risk factors for postoperative seizures after meningioma surgery are sparse and can be basically taken from preoperative imaging. Among surgical complications, postoperative hemorrhage and hydrocephalus are strong seizure predictors.

Predicting the risk of postoperative recurrence and high-grade histology in patients with intracranial meningiomas using routine preoperative MRI.

Risk factors for prediction of prognosis in meningiomas derivable from routine preoperative magnetic resonance imaging (pMRI) remain elusive. Correlations of tumor and edema volume, disruption of the arachnoid layer, heterogeneity of contrast enhancement, enhancement of the capsule, T2-intensity, tumor shape, and calcifications on pMRI with tumor recurrence and high-grade (WHO grade II/III) histology were analyzed in 565 patients who underwent surgery for WHO grade I (N = 516, 91%) or II/III (high-grade histology, N = 49, 9%) meningioma between 1991 and 2018. Edema volume (OR, 1.00; p = 0.003), heterogeneous contrast enhancement (OR, 3.10; p < 0.001), and an irregular shape (OR, 2.16; p = 0.015) were associated with high-grade histology. Multivariate analyses confirmed edema volume (OR, 1.00; p = 0.037) and heterogeneous contrast enhancement (OR, 2.51; p = 0.014) as risk factors for high-grade histology. Tumor volume (HR, 1.01; p = 0.045), disruption of the arachnoid layer (HR, 2.50; p = 0.003), heterogeneous contrast enhancement (HR, 2.05; p = 0.007), and an irregular tumor shape (HR, 2.57; p = 0.001) were correlated with recurrence. Multivariate analyses confirmed tumor volume (HR, 1.01; p = 0.032) and disruption of the arachnoid layer (HR, 2.44; p = 0.013) as risk factors for recurrence, independent of histology. Subgroup analyses revealed disruption of the arachnoid layer (HR, 9.41; p < 0.001) as a stronger risk factor for recurrence than high-grade histology (HR, 5.15; p = 0.001). Routine pMRI contains relevant information about the risk of recurrence or high-grade histology of meningioma patients. Loss of integrity of the arachnoid layer on MRI had a higher prognostic value than the WHO grading, and underlying histological or molecular alterations remain to be determined.

The Simpson grading: defining the optimal threshold for gross total resection in meningioma surgery.

Classification of the extent of resection into gross and subtotal resection (GTR and STR) after meningioma surgery is derived from the Simpson grading. Although utilized to indicate adjuvant treatment or study inclusion, conflicting definitions of STR in terms of designation of Simpson grade III resections exist. Correlations of Simpson grading and dichotomized scales (Simpson grades I-II vs ≥ III and grade I-III vs ≥ IV) with postoperative recurrence/progression were compared using Cox regression models. Predictive values were further compared by time-dependent receiver operating curve (tdROC) analyses. In 939 patients (28% males, 72% females) harboring WHO grade I (88%) and II/III (12%) meningiomas, Simpson grade I, II, III, IV, and V resections were achieved in 29%, 48%, 11%, 11%, and < .5%, respectively. Recurrence/progression was observed in 112 individuals (12%) and correlated with Simpson grading (p = .003). The risk of recurrence/progression was increased after STR in both dichotomized scales but higher when subsuming Simpson grade ≥ IV than grade ≥ III resections (HR: 2.49, 95%CI 1.50-4.12; p < .001 vs HR: 1.67, 95%CI 1.12-2.50; p = .012). tdROC analyses showed moderate predictive values for the Simpson grading and significantly (p < .05) lower values for both dichotomized scales. AUC values differed less between the Simpson grading and the dichotomization into grade I-III vs ≥ IV than grade I-II vs ≥ III resections. Dichotomization of the extent of resection is associated with a loss of the prognostic value. The value for the prediction of progression/recurrence is higher when dichotomizing into Simpson grade I-III vs ≥ IV than into grade I-II vs ≥ III resections.

Occurrence of Fibrotic Tumor Vessels in Grade I Meningiomas Is Strongly Associated with Vessel Density, Expression of VEGF, PlGF, IGFBP-3 and Tumor Recurrence.

Angiogenesis is a key feature during oncogenesis and remains a potential target of antiangiogenic therapy. While commonly described in high-grade lesions, vascularization and its correlation with prognosis in grade I meningiomas is largely unexplored. In the histological classification, not only the number but also the composition of blood vessels seems to be important. Therefore, tumor vessel density and fibrosis were correlated with clinical and imaging variables and prognosis in 295 patients with intracranial grade I meningioma. Expression of pro-angiogenic proteins within the meningiomas was investigated by proteome analyses and further validated by immunohistochemical staining. Fibrotic tumor vessels (FTV) were detected in 48% of all tumors and strongly correlated with vessel density, but not with the histopathological tumor subtype. Occurrence of FTV was correlated with a 2-fold increased risk of recurrence in both univariate and multivariate analyses. Explorative proteome analyses revealed upregulation of VEGF (vascular endothelial growth factor), PlGF (placental growth factor), and IGFBP-3 (insulin-like growth factor-binding protein-3) in tumors displaying FTV. Immunohistochemical analyses confirmed strong correlations between tumor vessel fibrosis and expression of VEGF, PlGF, and IGFBP-3. Presence of FTV was strongly associated with disruption of the arachnoid layer on preoperative MRI in univariate and multivariate analyses. In summary, the occurrence of fibrotic tumor vessels in grade I meningiomas is strongly associated with vessel density, disruption of the arachnoid layer, expression of VEGF, PlGF, IGFBP-3 and tumor recurrence.