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.

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.

Clinical, radiological, and histopathological predictors for long-term prognosis after surgery for atypical meningiomas.

BACKGROUND: Despite considerable rates of recurrence and mortality in atypical meningiomas, reliable predictors for estimating postoperative long-term prognosis remain elusive. METHODS: Clinical, histopathological, and radiological variables from 138 patients, including 64 females and 74 males (46% and 54%, median age 62 years), who underwent surgery for intracranial atypical meningioma were retrospectively analyzed. Associations between variables and recurrence and mortality were investigated using uni- and multivariate analyses. RESULTS: Gross total (GTR) and subtotal resection (STR) was achieved in 81% and 19% of cases, respectively. Within a median follow-up of 62 months, recurrence occurred in 52 (38%) and mortality in 22 (16%) cases. In patients who did not receive adjuvant irradiation, recurrence rates were higher after STR than after GTR (32% vs 63%, p = 0.025). In univariate analyses, only intratumoral calcifications on preoperative MRI (p = 0.012) and the presence of brain invasion in the absence of other histological grading criteria (p = 0.010) were correlated with longer progression-free intervals (PFI). In multivariate analyses, patient age was positively (HR 1.03, 95%CI 1.04-1.05; p = 0.018) and the presence of brain invasion as the only grading criterion (HR 0.37, 95%CI 0.19-0.74; p = 0.005) was negatively related with progression, while rising age at the time of surgery (HR 1.07, 95%CI 1.03-1.12; p = 0.001) was prognostic for mortality. CONCLUSIONS: PFI was longer in brain invasive but otherwise histological benign meningiomas and in tumors displaying calcifications on preoperative MRI. Advancing patient age and lower Karnofsky Performance Score were associated with higher overall mortality.

The Simpson grading in meningioma surgery: does the tumor location influence the prognostic value?

In meningiomas, location-specific differences of the prognostic value of the Simpson classification are sparsely investigated but can influence strategy of surgery. We therefore compared the prognostic value of the Simpson classification in different tumor locations. Progression was compared with Simpson grade in 826 meningioma patients (median age 58 years, female:male ratio 2.4) in location-specific uni- and multivariate analyses. Simpson grade strongly correlated with tumor location (p < .001). Within a median follow-up of 50 months, recurrence was observed in 107 of 803 patients (13%). In general, increasing Simpson grade (p = .002) and subtotal resection (STR, ≥grade III) were correlated with tumor recurrence [hazard ratio (HR): 1.87; p = .004]. In 268 convexity meningiomas, frequency of tumor recurrence correlated with Simpson grade (p = .034). Risk of recurrence was similar after grade I and II resections, tended to increase after grade III (HR: 2.35; p = .087) but was higher after grade IV resections (HR: 7.35; p = .003). Risk of recurrence was higher after STR (HR: 4.21; p = .001) than after gross total resection (GTR, ≤grade II). Contrarily, increasing Simpson grade and STR were not correlated with progression in 102 falx, 38 posterior fossa and nine intraventricular meningiomas. In 325 skull base lesions, risk of recurrence was similar after GTR and STR (p = .198) and was only increased after grade IV resections (HR: 3.26; p = .017). Simpson grading and extent of resection were not equally prognostic in all locations. Lower impact of extent of resection should be considered during surgery for skull base, posterior fossa and falx meningiomas.

Risk factors for preoperative seizures in intracranial meningiomas.

BACKGROUND: About 25% of patients with intracranial meningioma display seizures at the time of initial presentation. Hence, identification of risk factors for preoperative seizures is crucial during perioperative care of meningioma patients. METHODS: Associations of preoperative seizures with clinical, radiological and histological variables were analyzed in 945 patients (689 females, 73% and 256 males, 27%; median age: 58 years) who underwent surgery for primary diagnosed intracranial meningioma. RESULTS: Preoperative seizures were found in 189 patients (20%). In univariate analyses, male gender (OR=1.91, 95% CI: 1.37-2.68; P<0.001), grade II/III histology (OR=2.24, 95% CI: 1.46-3.46; P<0.001), brain invasion (OR=2.59, 95% CI: 1.45-4.63; P=001), non-skull base tumor location (OR=3.07, 95% CI: 2.13-4.41; P<0.001), heterogeneous contrast-enhancement (OR=1.60, 95% CI: 1.04-2.46; P=0.031), intratumoral calcifications (OR=1.91, 95% CI: 1.17-3.10; P=0.009), an irregular shape (OR=2.07, 95% CI: 1.32-3.26; P=0.002) as well as tumor (OR=1.01 per ccm, 95% CI: 1.00-1.02; P=0.001) and edema volumes (OR=1.01 per ccm, 95% CI: 1.00-1.01; P<0.001) were correlated with seizures. Semiology was not related to any of the analyzed variables (P>0.05, each). No associations were found between seizures and histological subtype of 832 grade I meningiomas (P=0.391). In multivariate analyses, only non-skull base tumor location (OR=3.12, 95% CI: 1.74-5.59; P<0.001) and a rising peritumoral edema volume (OR=1.01 per ccm, 95% CI: 1.00-1.01; P<0.001) were identified as independent predictors for preoperative seizures. CONCLUSIONS: Several mostly radiological variables were identified as risk factors for epilepsy. However, multivariate analyses confirmed only peritumoral edema and non-skull base tumor location as independent predictors for preoperative seizures. None of the variables predicts semiology.

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.

Risk of tumor recurrence in intracranial meningiomas: comparative analyses of the predictive value of the postoperative tumor volume and the Simpson classification.

OBJECTIVE: In meningiomas, the Simpson grading system is applied to estimate the risk of postoperative recurrence, but might suffer from bias and limited overview of the resection cavity. In contrast, the value of the postoperative tumor volume as an objective predictor of recurrence is largely unexplored. The objective of this study was to compare the predictive value of residual tumor volume with the intraoperatively assessed extent of resection (EOR). METHODS: The Simpson grade was determined in 939 patients after surgery for initially diagnosed intracranial meningioma. Tumor volume was measured on initial postoperative MRI within 6 months after surgery. Correlation between both variables and recurrence was compared using a tree-structured Cox regression model. RESULTS: Recurrence correlated with Simpson grading (p = 0.003). In 423 patients (45%) with available imaging, residual tumor volume covered a broad range (0-78.5 cm3). MRI revealed tumor remnants in 8% after gross-total resection (Simpson grade I-III, range 0.12-33.5 cm3) with a Cohen's kappa coefficient of 0.7153. Postoperative tumor volume was correlated with recurrence in univariate analysis (HR 1.05 per cm3, 95% CI 1.02-1.08 per cm3, p < 0.001). A tree-structured Cox regression model revealed any postoperative tumor volume > 0 cm3 as a critical cutoff value for the prediction of relapse. Multivariate analysis confirmed the postoperative tumor volume (HR 1.05, p < 0.001) but not the Simpson grading (p = 0.398) as a predictor for recurrence. CONCLUSIONS: EOR according to Simpson grading was overrated in 8% of tumors compared to postoperative imaging. Because the predictive value of postoperative imaging is superior to the Simpson grade, any residual tumor should be carefully considered during postoperative care of meningioma patients.

Brain invasion and the risk of seizures in patients with meningioma.

OBJECTIVE: Identification of risk factors for perioperative epilepsy remains crucial in the care of patients with meningioma. Moreover, associations of brain invasion with clinical and radiological variables have been largely unexplored. The authors hypothesized that invasion of the cortex and subsequent increased edema facilitate seizures, and they compared radiological data and perioperative seizures in patients with brain-invasive or noninvasive meningioma. METHODS: Correlations of brain invasion with tumor and edema volumes and preoperative and postoperative seizures were analyzed in univariate and multivariate analyses. RESULTS: Totals of 108 (61%) females and 68 (39%) males with a median age of 60 years and harboring totals of 92 (52%) grade I, 79 (45%) grade II, and 5 (3%) grade III tumors were included. Brain invasion was found in 38 (22%) patients and was absent in 138 (78%) patients. The tumors were located at the convexity in 72 (41%) patients, at the falx cerebri in 26 (15%), at the skull base in 69 (39%), in the posterior fossa in 7 (4%), and in the ventricle in 2 (1%); the median tumor and edema volumes were 13.73 cm3 (range 0.81-162.22 cm3) and 1.38 cm3 (range 0.00-355.80 cm3), respectively. As expected, edema volume increased with rising tumor volume (p < 0.001). Brain invasion was independent of tumor volume (p = 0.176) but strongly correlated with edema volume (p < 0.001). The mean edema volume in noninvasive tumors was 33.0 cm3, but in invasive tumors, it was 130.7 cm3 (p = 0.008). The frequency of preoperative seizures was independent of the patients' age, sex, and tumor location; however, the frequency was 32% (n = 12) in patients with invasive meningioma and 15% (n = 21) in those with noninvasive meningioma (p = 0.033). In contrast, the probability of detecting brain invasion microscopically was increased more than 2-fold in patients with a history of preoperative seizures (OR 2.57, 95% CI 1.13-5.88; p = 0.025). In univariate analyses, the rate of preoperative seizures correlated slightly with tumor volume (p = 0.049) but strongly with edema volume (p = 0.014), whereas seizure semiology was found to be independent of brain invasion (p = 0.211). In multivariate analyses adjusted for age, sex, tumor location, tumor and edema volumes, and WHO grade, rising tumor volume (OR 1.02, 95% CI 1.00-1.03; p = 0.042) and especially brain invasion (OR 5.26, 95% CI 1.52-18.15; p = 0.009) were identified as independent predictors of preoperative seizures. Nine (5%) patients developed new seizures within a median follow-up time of 15 months after surgery. Development of postoperative epilepsy was independent of all clinical variables, including Simpson grade (p = 0.133), tumor location (p = 0.936), brain invasion (p = 0.408), and preoperative edema volume (p = 0.081), but was correlated with increasing preoperative tumor volume (p = 0.004). Postoperative seizure-free rates were similar among patients with invasive and those with noninvasive meningioma (p = 0.372). CONCLUSIONS: Brain invasion was identified as a new and strong predictor for preoperative, but not postoperative, seizures. Although also associated with increased peritumoral edema, seizures in patients with invasive meningioma might be facilitated substantially by cortical invasion itself. Consideration of seizures in consultations between the neurosurgeon and neuropathologist can improve the microscopic detection of brain invasion.