Frailty in intracranial meningioma resection: the risk analysis index demonstrates strong discrimination for predicting non-home discharge and in-hospital mortality.

PURPOSE: Frailty is an independent risk factor for adverse postoperative outcomes following intracranial meningioma resection (IMR). The role of the Risk Analysis Index (RAI) in predicting postoperative outcomes following IMR is nascent but may inform preoperative patient selection and surgical planning. METHODS: IMR patients from the Nationwide Inpatient Sample were identified using diagnostic and procedural codes (2019-2020). The relationship between preoperative RAI-measured frailty and primary outcomes (non-home discharge (NHD), in-hospital mortality) and secondary outcomes (extended length of stay (eLOS), complication rates) was assessed via multivariate analyses. The discriminatory accuracy of the RAI for primary outcomes was measured in area under the receiver operating characteristic (AUROC) curve analysis. RESULTS: A total of 23,230 IMR patients (mean age = 59) were identified, with frailty statuses stratified by RAI score: 0-20 "robust" (R)(N = 10,665, 45.9%), 21-30 "normal" (N)(N = 8,895, 38.3%), 31-40 "frail" (F)(N = 2,605, 11.2%), and 41+ "very frail" (VF)(N = 1,065, 4.6%). Rates of NHD (R 11.5%, N 29.7%, F 60.8%, VF 61.5%), in-hospital mortality (R 0.5%, N 1.8%, F 3.8%, VF 7.0%), eLOS (R 13.2%, N 21.5%, F 40.9%, VF 46.0%), and complications (R 7.5%, N 11.6%, F 15.7%, VF 16.0%) significantly increased with increasing frailty thresholds (p < 0.001). The RAI demonstrated strong discrimination for NHD (C-statistic: 0.755) and in-hospital mortality (C-statistic: 0.754) in AUROC curve analysis. CONCLUSION: Increasing RAI-measured frailty is significantly associated with increased complication rates, eLOS, NHD, and in-hospital mortality following IMR. The RAI demonstrates strong discrimination for predicting NHD and in-hospital mortality following IMR, and may aid in preoperative risk stratification.

Comprehensive assessment of atypical and anaplastic pediatric meningiomas utilizing national cancer database: a retrospective cohort study.

PURPOSE: To examine demographic and clinical characteristics and their association with survival in grade 2 and 3 pediatric meningiomas in a large cohort using the National Cancer Database (NCDB). METHODS: We conducted a comprehensive analysis using data from NCDB between 2004 to 2018. Tumor-specific data included tumor grade and size. Treatment details, including surgical resection, extent of resection, and radiotherapy, were gathered. Our analytic approach incorporated logistic and Poisson regression, Kaplan-Meier survival estimates, and Cox proportional hazards models. RESULTS: Among the included 239 patients aged 0-21 years, age category distribution was significantly different between grade 2 and grade 3 tumors (p = 0.018). For grade 2 meningiomas, 51.5% of patients were female, and 76.7% were white. 85.3% of patients with grade 2 meningiomas underwent surgical resection, of which 67% underwent gross total resection. Overall survival (OS) was significantly different between resected and non-resected patients (p = 0.048). Uninsured patients were over seven times as likely to have prolonged length of stay (LOS) versus those with private insurance (OR = 7.663, p = 0.014). For grade 3 meningiomas, 51.4% of patients were male, and 82.9% were white. 91.4% of patients with grade 3 meningiomas underwent surgical resection, of which 53.3% underwent subtotal resection. OS was not significantly different between resected and non-resected patients (p = 0.659). CONCLUSION: In summary, there were significant differences in age, maximum tumor dimension, unplanned readmission, radiotherapy, and treatment combinations between grade 2 and 3 meningiomas. These findings highlight the intricacies of managing pediatric meningiomas and emphasize the necessity for tailored therapeutic approaches to enhance outcomes in the future.

Atypical and anaplastic meningiomas in the later decades of life: A national cancer database analysis.

PURPOSE: We conducted a National Cancer Database (NCDB) study to investigate the epidemiological characteristics and identify predictors of outcomes associated with geriatric meningiomas. METHODS: The NCDB was queried for adults aged 60-89 years diagnosed between 2010 and 2017 with grade 2 and 3 meningiomas. The patients were classified into three age groups based on their age: 60-69 (hexagenarians), 70-79 (septuagenarians), and 80-89 (octogenarians). The log-rank test was utilized to compare the differences in overall survival (OS). Univariate and multivariate Cox proportional hazards regressions were used to evaluate the mortality risk associated with various patient and disease parameters. RESULTS: A total of 6585 patients were identified. Hexagenerians were the most common age group (49.8%), with the majority of meningiomas being classified as grade 2 (89.5%). The incidence of high-grade meningiomas increased in all age groups during the study period. Advanced age, male sex, black race, lower socioeconomic status, Charlson-Deyo score ≥ 2, and higher tumor grade were independent factors of poor survival. Among the modes of treatment, the extent of surgical resection, adjuvant radiotherapy, and treatment at a noncommunity cancer program were linked with better outcomes. CONCLUSION: In geriatric patients with high-grade meningiomas, the greater extent of surgical resection and radiotherapy are associated with improved survival. However, the management and outcome of geriatric patients with higher-grade meningiomas are also associated with several socioeconomic factors.

Eribulin prolongs survival in an orthotopic xenograft mouse model of malignant meningioma.

Meningioma is the most common intracranial tumor, with generally favorable patient prognosis. However, patients with malignant meningioma typically experience recurrence, undergo multiple surgical resections, and ultimately have a poor prognosis. Thus far, effective chemotherapy for malignant meningiomas has not been established. We recently reported the efficacy of eribulin (Halaven) for glioblastoma with a telomerase reverse transcriptase (TERT) promoter mutation. This study investigated the anti-tumor effect of eribulin against TERT promoter mutation-harboring human malignant meningioma cell lines in vitro and in vivo. Two meningioma cell lines, IOMM-Lee and HKBMM, were used in this study. The strong inhibition of cell proliferation by eribulin via cell cycle arrest was demonstrated through viability assay and flow cytometry. Apoptotic cell death in malignant meningioma cell lines was determined through vital dye assay and immunoblotting. Moreover, a wound healing assay revealed the suppression of tumor cell migration after eribulin exposure. Intraperitoneal administration of eribulin significantly prolonged the survival of orthotopic xenograft mouse models of both malignant meningioma cell lines implanted in the subdural space (P < .0001). Immunohistochemistry confirmed apoptosis in brain tumor tissue treated with eribulin. Overall, these results suggest that eribulin is a potential therapeutic agent for malignant meningiomas.

Survival of brain tumour patients with epilepsy.

Pro-tumorigenic electrochemical synapses between neurons and brain tumour cells in preclinical studies suggest unfavourable effects of epilepsy on patient survival. We investigated associations of epilepsy and survival in three cohorts of brain tumour patients (meningioma, glioblastoma and brain metastases). Cohorts were segregated into three groups for comparative analyses: (i) no epilepsy; (ii) epilepsy without status epilepticus; and (iii) status epilepticus. Status epilepticus was considered a surrogate of extensive neuronal hyperexcitability. The main outcome was progression-free survival (meningioma) and overall survival (glioblastoma and brain metastases), adjusted for established prognostic factors and onset of epilepsy by time-dependent multivariate Cox modelling. The primary analysis population comprised 1792 patients (742 meningioma, 249 glioblastoma, 801 brain metastases). Epilepsy was associated with favourable prognostic factors. However, on multivariate analyses, status epilepticus was associated with inferior overall survival of patients with glioblastoma [status epilepticus versus no epilepsy multivariate hazard ratio (HR) 3.72, confidence interval (CI) 1.78-7.76, P < 0.001] and brain metastases (status epilepticus versus no epilepsy HR 2.30, CI 1.10-4.79, P = 0.026). Among brain metastases patients, but not among patients with meningioma or glioblastoma, epilepsy was similarly associated with inferior overall survival (epilepsy versus no epilepsy HR 2.16, CI 1.60-2.93, P < 0.001). We conclude that epilepsy may convey inferior survival of patients with malignant brain tumours.

Metabolic alterations in meningioma reflect the clinical course.

BACKGROUND: Meningiomas are common brain tumours that are usually defined by benign clinical course. However, some meningiomas undergo a malignant transformation and recur within a short time period regardless of their World Health Organization (WHO) grade. The current study aimed to identify potential markers that can discriminate between benign and malignant meningioma courses. METHODS: We profiled the metabolites from 43 patients with low- and high-grade meningiomas. Tumour specimens were analyzed by nuclear magnetic resonance analysis; 270 metabolites were identified and clustered with the AutoPipe algorithm. RESULTS: We observed two distinct clusters marked by alterations in glycine/serine and choline/tryptophan metabolism. Glycine/serine cluster showed significantly lower WHO grades and proliferation rates. Also progression-free survival was significantly longer in the glycine/serine cluster. CONCLUSION: Our findings suggest that alterations in glycine/serine metabolism are associated with lower proliferation and more recurrent tumours. Altered choline/tryptophan metabolism was associated with increases proliferation, and recurrence. Our results suggest that tumour malignancy can be reflected by metabolic alterations, which may support histological classifications to predict the clinical outcome of patients with meningiomas.

Clear cell histology portends a worse prognosis than other WHO grade II histologies.

PURPOSE: Clear cell meningioma (CCM) is a rare WHO grade II meningioma variant, characterized by aggressive features and a high tumor recurrence rate. In this study, we compared overall and progression-free survivals between CCMs and other WHO grade II meningiomas. METHODS: A retrospective institutional database review was performed to identify all patients who underwent surgical resection of a WHO grade II meningioma between 1997 and 2019. Overall survival and progression-free survival were compared between patients with clear cell meningiomas and patients with other WHO grade II meningiomas. Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and survival. RESULTS: We included a total of 214 patients in this study (43 CCMs, 171 other WHO grade II meningiomas). Patients with CCMs had significantly shorter progression-free (p = 0.001) and overall (p = 0.026) survivals than patients with other grade II meningiomas. In multivariable analysis, clear cell histology was a significant and powerful independent predictor of tumor recurrence (HR 1.93; 95% CI 1.14-3.26) when controlling for tumor location, extent of resection, and adjuvant radiation. In multivariable analysis, clear cell histology correlated with increased mortality (HR 1.96, 95% CI 0.97-3.94), though this was not statistically significant. CONCLUSION: This is the first study to compare overall and progression-free survivals between CCMs and other WHO grade II meningiomas. Clear cell histology predicts a higher risk of tumor recurrence and mortality than other grade II histologies. Future studies may help to understand the impact of these findings and the treatment implications.

Extent of resection and survival outcomes in World Health Organization grade II meningiomas.

PURPOSE: WHO grade II meningiomas behave aggressively, with recurrence rates as high as 60%. Although complete resection in low-grade meningiomas is associated with a relatively low recurrence rate, the impact of complete resection for WHO grade II meningiomas is less clear. We studied the association of extent of resection with overall and progression-free survivals in patients with WHO grade II meningiomas. METHODS: A retrospective database review was performed to identify all patients who underwent surgical resection for intracranial WHO grade II meningiomas at our institution between 1995 and 2019. Kaplan-Meier analysis was used to compare overall and progression-free survivals between patients who underwent gross total resection (GTR) and those who underwent subtotal resection (STR). Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and mortality. RESULTS: Of 214 patients who underwent surgical resection for WHO grade II meningiomas (median follow-up 53.4 months), 158 had GTR and 56 had STR. In Kaplan-Meier analysis, patients who underwent GTR had significantly longer progression-free (p = 0.002) and overall (p = 0.006) survivals than those who underwent STR. In multivariable Cox proportional-hazards analysis, GTR independently predicted prolonged progression-free (HR 0.57, p = 0.038) and overall (HR 0.44, p = 0.017) survivals when controlling for age, tumor location, and adjuvant radiation. CONCLUSIONS: Extent of resection independently predicts progression-free and overall survivals in patients with WHO grade II meningiomas. In an era of increasing support for adjuvant treatment modalities in the management of meningiomas, our data support maximal safe resection as the primary goal in treatment of these patients.

Volumetric growth rate of incidental asymptomatic meningiomas: a single-center prospective cohort study.

BACKGROUND: Decision about treatment of incidentally found intracranial meningiomas is controversial and conditioned by the growth potential of these tumors. We aimed to evaluate the growth rate of a cohort of incidentally found asymptomatic meningiomas and to analyze their natural course and the need for eventual treatment. METHODS: A total of 193 patients harboring intracranial meningiomas (85 with 109 incidental and 108 with 112 symptomatic) were included between 2015 and 2019. In the prospective cohort of incidental meningiomas, we measured size at diagnosis, volumetric growth rate (by segmentation software), appearance of symptoms, and need for surgery or radiotherapy. Progression-free survival and risk factors for growth were assessed with Kaplan-Meier survival and Cox regression analyses. RESULTS: Among incidental meningiomas, 94/109 (86.2%) remained untreated during a median follow-up of 49.3 months. Tumor growth was observed in 91 (83.5%) and > 15% growth in 40 (36.7%). Neurological symptoms developed in 1 patient (1.2%). Volume increased an average of 0.51 cm3/year (95% CI, 0.20-0.82). Nine patients were operated (9.2%) and 4 underwent radiotherapy (4.7%). Treatment-related complication rates of incidental and symptomatic meningiomas were 0% and 35.4%, respectively. Persistent neurological defects occurred in 46 (40.7%) of symptomatic versus 2 (2.3%) of incidental meningiomas. Among covariates, only brain edema resulted in an increased risk of significant tumor growth in the female subgroup (Cox regression HR 2.96, 95% CI 1.02-8.61, p = 0.046). Size at diagnosis was significantly greater in the symptomatic meningioma group (37.33 cm3 versus 4.74 cm3, p < 0.001). CONCLUSIONS: Overall, 86% of incidentally found meningiomas remained untreated over the first 4 years of follow-up. The majority grew within the 20% range, yet very few developed symptoms. Treatment-related morbidity was absent in the incidental meningioma group.

Poor prognosis associated with TERT gene alterations in meningioma is independent of the WHO classification: an individual patient data meta-analysis.

BACKGROUND: TERT gene alterations (TERT-alt) have been linked to increased risk of recurrence in meningiomas, whereas the association to mortality largely remain incompletely investigated. As incongruence between clinical course and WHO grade exists, reliable biomarkers have been sought. METHODS: We applied the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data Statement. We compiled data from eight studies and allocated patients to TERT-alt (n=59) or TERT promoter wild-type (TERTp-wt; n=618). We compared the two groups stratified for WHO grades as: incidence rates, survival probabilities and cumulative recurrences. We estimated the effects of WHO grade, age at diagnosis and sex as HRs. RESULTS: TERT-alt occurred in 4.7%, 7.9% and 15.4% of WHO-I/WHO-II/WHO-III meningiomas, respectively. The median recurrence-free survival was 14 months for all TERT-alt patients versus 101 months for all TERTp-wt patients. The HR for TERT-alt was 3.74 in reference to TERTp-wt. For all TERT-alt patients versus all TERTp-wt patients, the median overall survival was 58 months and 160 months, respectively. The HR for TERT-alt was 2.77 compared with TERTp-wt. TERT-alt affected prognosis independent of WHO grades. Particularly, the recurrence rate was 4.8 times higher in WHO-I/-II TERT-alt patients compared with WHO-III TERTp-wt patients. The mortality rate was 2.7 times higher in the WHO-I and WHO-II TERT-alt patients compared with WHO-III TERTp-wt patients. CONCLUSIONS: TERT-alt is an important biomarker for significantly higher risk of recurrence and death in meningiomas. TERT-alt should be managed and surveilled aggressively. We propose that TERT-alt analysis should be implemented as a routine diagnostic test in meningioma and integrated into the WHO classification. TRIAL REGISTRATION NUMBER: PROSPERO: CRD42018110566.

Adjuvant radiation for WHO grade II and III intracranial meningiomas: insights on survival and practice patterns from a National Cancer Registry.

INTRODUCTION: WHO grades II (atypical) and III (malignant) meningiomas are associated with significant morbidity and mortality. The role of adjuvant radiotherapy (RT) in management remains controversial. The goal of this study was to evaluate the impact of adjuvant RT on 5-year survival in patients with atypical and malignant meningiomas. We secondarily aimed to assess contemporary practice patterns and the impact of sociodemographic factors on outcome. METHODS: We queried the National Cancer Database for patients ≥ 18 years of age with cranial atypical or malignant meningiomas from 2010 through 2015 who underwent surgical resection with or without adjuvant radiotherapy. Subjects with unknown WHO grade or radiation status and those not receiving any surgical procedure were excluded from analysis. RESULTS: The study includes 7486 patients, 6788 with atypical and 698 with malignant meningiomas. Overall 5-year survival was 76.9% (95% CI 75.5-78.3%) and 43.3% (95% CI 38.8-48.2%) among patients with WHO grades II and III meningiomas, respectively. Adjuvant RT correlated with improved survival in a multivariable model in patients with grade II tumors (HR 0.78; p = 0.029) regardless of the extent of resection. Age (HR 2.33; p < 0.001), male sex (HR 1.27; p < 0.001), Black race (HR 1.27; p = 0.011) and Charlson-Deyo Score ≥ 2 (1.35; p = 0.001) correlated with poorer survival whereas private insurance (HR 0.71; p < 0.001) correlated with improved survival. Adjuvant RT was also associated with improved 5-year survival among those with grade III tumors on univariate analysis (log-rank p = 0.006) but was underpowered for multivariable modeling. Utilization of adjuvant radiotherapy was only 28.4% and correlated with private insurance status. Academic institutions (25.3%) and comprehensive community cancer programs (21.4%) had lower radiotherapy utilization rates compared with integrated network cancer programs (30.5%) and community cancer programs (29.7%). CONCLUSIONS: Adjuvant RT may correlate with improved overall survival in patients with grades II and III intracranial meningiomas regardless of the extent of resection. There is poor utilization of adjuvant RT for patients with grades II and III meningiomas likely due to a paucity of quality data on the subject. These findings will be strengthened with prospective data evaluating the role of adjuvant RT.

Long-term outcomes of multimodality management for parasagittal meningiomas.

PURPOSE: The aim of this study was to systematically analyze the clinical characteristics of a large cohort of parasagittal meningioma (PM) and to evaluate the patients' outcomes and best treatment strategies based on tumor features. METHODS: To minimize selection bias we performed a single-institutional review of PM with restricted criteria. One hundred and ninety-two consecutive patients who met criteria for inclusion were reviewed from 2003 to 2011 in our general hospital. RESULTS: A total of 131 cases (68.2%) were with WHO grade I, while grade II and grade III PMs constituted 40 (20.8%) and 21 cases (10.9%). Higher histological grade was associated with loss of trimethylation of H3K27 (P = 0.000). For WHO grade I PMs, GTR was significantly associated with a better PFS (P = 0.023); however, adjuvant radiotherapy did not benefit patients with STR (P = 0.215). For de novo high-grade (WHO grade II and III) PMs (n = 37), adjuvant radiotherapy was associated with a significantly longer OS (P = 0.013), while no difference was observed between GTR and STR (P = 0.654). In recurrent high-grade PM patients (n = 24), GTR combined with adjuvant radiotherapy increased PFS (P = 0.005). CONCLUSIONS: This study demonstrated that PMs were a heterogeneous group of tumors with a high proportion of high-grade tumors that often displayed aggressive clinical behaviors. Low-grade PM benefited from radical resection, whereas high-grade de novo PM did not. Adjuvant radiotherapy significantly prolonged OS for high-grade primary PM, but did not impact survival of patients with subtotally resected low-grade tumors. Long-term outcome of high-grade recurrent PMs was dismal. We thus show that extent of tumor resection, tumor grade and tumor recurrent status inform therapeutic decisions for PMs.

Multiple meningiomas: does quantity matter? a population-based survival analysis with underlined age and sex differences.

INTRODUCTION: Intracranial meningiomas rarely present with multiple lesions. To the best of our knowledge, current literature regarding meningiomatosis (MM) is mostly comprised of small case series and individual reports. Hence, survival outcome data are limited. The Objective of this study is to explore the influence of sex, age, and number of lesions on overall survival (OS) in patients with MM. METHODS: We obtained demographic and clinical data from the surveillance, epidemiology, and end results program (SEER) on adult patients diagnosed with meningiomas from 1975 to 2017. Univariable and multivariable analyses were conducted to assess whether number of lesions, age, and sex had a significant influence on OS. RESULTS: 99,918 cases were included. Results showed that MM patients had a significantly decreased OS when compared to patients with a single lesion (median OS of 94 and 180 months, respectively; p < 0.001). Further analysis showed a progressive decrease on OS for every additional lesion; 2 (HR 1.659 [CI 95% 1.612-1.708], p < 0.001), 3 (HR 1.877 [CI 95% 1.773-1.988], p < 0.001), and ≥ 4 (HR 2.116 [CI 95% 1.886-2.373], p < 0.001). When assessing for sex differences, female patients had increased OS (HR 0.778 [CI 95% 0.743-0.815], p < 0.001) and decreased risk of developing MM (HR 0.809 [CI 95% 0.784-0.835], p < 0.001). CONCLUSION: Increasing number of meningiomas has a significant negative impact on OS, with a progressive decrease on survival for every additional lesion. Furthermore, female patients had increased OS and decreased risk to develop MM.

Racial and socioeconomic correlates of treatment and survival among patients with meningioma: a population-based study.

BACKGROUND: Though meningioma is the most common primary brain tumor, there is a paucity of epidemiologic studies investigating disparities in treatment and patient outcomes. Therefore, we sought to explore how sociodemographic factors are associated with rates of gross total resection (GTR) and radiotherapy as well as survival. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was queried to identify adult patients with meningioma diagnosed between 2005 and 2015. Socioeconomic status (SES) was determined using a validated composite index in which patients were stratified into tertiles and quintiles. Multivariable logistic regression and Cox proportional hazards analyses were used to identify predictors of treatment and survival, respectively. RESULTS: 71,098 patients met our inclusion criteria. Low SES quintile was associated with reduced odds of receiving GTR (OR 0.76, 95% CI 0.69-0.83, p < 0.0001) and radiotherapy (OR 0.83, 95% CI 0.76-0.91, p < 0.0001) as well as worse survival (HR 1.48, 95% CI 1.41-1.56) as compared to the highest SES quintile. Black patients had reduced odds of GTR (OR 0.74, 95% CI 0.67-0.71, p < 0.0001) and worse survival (HR 1.23, 95% CI 1.18-1.29, p < 0.0001) as compared to white patients. CONCLUSIONS: This national study of patients with meningioma found socioeconomic status and race to be independent inverse correlates of likelihood of GTR, radiotherapy, and survival. Limited access to care may underlie these disparities in part, and future studies are warranted to identify specific causes for these findings.

Impact of postoperative radiotherapy on recurrence of primary intracranial atypical meningiomas.

BACKGROUND: Atypical meningiomas (WHO grade II) have high recurrence rate. However, data on the effect of radiotherapy (RT) is still conflicting. The aim of this study was to evaluate the influence of postoperative RT on the recurrence of primary atypical intracranial meningiomas. METHODS: The medical records of all patients who underwent surgery (2007-2017 in 4 neurosurgical departments) for a histologically diagnosed primary atypical meningioma were reviewed to assess progression-free survival (PFS) and prognostic factors. RESULTS: This analysis included 258 patients with a median age of 60 years (54.7% female). The predominant tumor locations were convexity and falx (60.9%) followed by the skull base (37.2%). Simpson grade I-II resection was achieved in 194 (75.2%) patients, Simpson grade III-IV in 53 patients (20.5%). Tumor progressed in 54 cases (20.9%). Postoperative RT was performed in 46 cases (17.8%). RT was more often applied after incomplete resection (37.7% vs. 13.4% Simpson III-IV vs. I-II). A multivariate analysis showed a significantly shorter PFS associated with Simpson III-IV [HR 1.19, (95% CI) 1.09-1.29, p < 0.001] and age > 65 years [HR 2.89, (95% CI) 1.56-5.33, p = 0.001]. A subgroup analysis with a minimal follow-up of 36 months revealed that Simpson III-IV [HR 3.01, 95% CI 1.31-6.931.03-1.24, p = 0.009] and age > 65 years [HR 2.48, 95% CI 1.20-5.13, p = 0.014] reduced PFS. The impact of postoperative RT on PFS remained statistically insignificant, even in a propensity-score matched survival analysis [n = 46; p = 0.438; OR 0.710 (0.299-1.687)]. CONCLUSIONS: In the present study, postoperative RT did not improve PFS. The most important prognostic factors remain the extent of resection and age.

Brachytherapy with surgical resection as salvage treatment for recurrent high-grade meningiomas: a matched cohort study.

PURPOSE: To evaluate surgical resection with brachytherapy placement as a salvage treatment in patients with recurrent high-grade meningioma who exhausted prior external beam treatment options. METHODS: Single-center retrospective review of our institutional experience of brachytherapy implantation from 2012 to 2018. The primary outcome of the study was progression free survival (PFS). Secondary outcomes included overall survival (OS) and complications. A matched cohort of patients not treated with brachytherapy over the same time period was evaluated as a control group. All patients had received prior radiation treatment and underwent planned gross total resection (GTR) surgery. RESULTS: A total of 27 cases were evaluated. Compared with prior treatment, brachytherapy implantation demonstrated a statistically significant improvement in tumor control [HR 0.316 (0.101 - 0.991), p = 0.034]. PFS-6 and PFS-12 were 92.3% and 84.6%, respectively. Compared with the matched control cohort, brachytherapy treatment demonstrated improved PFS [HR 0.310 (0.103 - 0.933), p = 0.030]. Overall survival was not statistically significantly different between groups [HR 0.381 (0.073 - 1.982), p = 0.227]. Overall postoperative complications were comparable between groups, although there was a higher incidence of radiation necrosis in the brachytherapy cohort. CONCLUSION: Brachytherapy with planned GTR improved PFS in recurrent high-grade meningioma patients who exhausted prior external beam radiation treatment options. Future improvement of brachytherapy dose delivery methods and techniques may continue to prolong control rates and improve outcomes for this challenging group of patients.

Effect of seizure timing on long-term survival in patients with brain tumor.

OBJECTIVE: Seizures often occur in patients with primary brain tumor (BT). The aim of this study was to determine if there is an association between the time of occurrence of seizures during the course of BT and survival of these patients. METHODS: This retrospective cohort study at Henry Ford Hospital, an urban tertiary referral center, included all patients who were diagnosed with primary BTs at Henry Ford Health System between January 2006 and December 2014. Timing of seizure occurrence, if occurred at presentation or after the tumor diagnosis during follow-up period, in different grades of BTs, and survival of these patients were analyzed. RESULTS: Of the 901 identified patients, 662 (53% male; mean age: 56 years) were included in final analysis, and seizures occurred in 283 patients (43%). Patients with World Health Organization (WHO) grade III BT with seizures as a presenting symptom only had better survival (adjusted hazard ratio (HR): 0.27; 95% confidence interval (CI), 0.11-0.67; P = 0.004). Seizures that occurred after tumor diagnosis only (adjusted HR: 2.11; 95% CI, 1.59-2.81; P < 0.001) in patients with WHO grade II tumors (adjusted HR: 3.41; 95% CI, 1.05-11.1; P = 0.041) and WHO grade IV tumors (adjusted HR: 2.14; 95% CI, 1.58-2.90; P < 0.001) had higher mortality. Seizures that occurred at presentation and after diagnosis also had higher mortality (adjusted HR: 1.34; 95% CI, 1.00-1.80; P = 0.049), in patients with meningioma (adjusted HR: 6.19; 95% CI, 1.30-29.4; P = 0.021) and grade III tumors (adjusted HR: 6.19; 95% CI, 2.56-15.0; P < 0.001). CONCLUSION: Seizures occurred in almost half of the patients with BTs. The association between seizures in patients with BT and their survival depends on the time of occurrence of seizures, if occurring at presentation or after tumor diagnosis, and the type of tumor. Better survival was noted in patients with WHO grade III BTs who had seizures at presentation at the time of diagnosis, while higher mortality was noted in WHO grade II tumors who had seizure at presentation and after tumor diagnosis, and in grade IV tumors after tumor diagnosis.

Clinical and histopathological predictors of outcome in malignant meningioma.

We investigated possible clinical and histopathological prognostic factors in a malignant meningioma cohort with comprehensive long-term population-based follow-up data. Twenty-four consecutive patients treated surgically for malignant meningioma at the Department of Neurosurgery and the Department of Pathology, Rigshospitalet, Copenhagen, Denmark, from December 2000 to March 2014 were retrospectively evaluated regarding progression-free survival (PFS) and overall survival (OS). Clinical parameters were recorded. All specimens underwent immunohistochemical analysis for Ki-67 and phosphohistone-H3 (PHH3). Prognostication was assessed with Cox proportional hazard regression analysis. The median follow-up was 46.1 months (range 0.7-150.7). The median progression-free survival was 16.5 months (95% CI 11.4-43.0) and the median overall survival was 46.6 months (95% CI 20.4-NA). Six patients were alive at the end of follow-up; two of these had not experienced a recurrence. No clinical parameter showed significant association with PFS or OS. Mitotic index (MI) was significantly associated with PFS and OS, and PHH3 MI with PFS. Immunohistochemical reactivity of Ki-67 > 10% was a negative predictor of PFS (HR 3.92, 95% CI 1.47-10.4, p = 0.0063) and OS (HR 3.35, 95% CI 1.12-10.1, p = 0.0313). The histological subgrouping of grade III meningioma into anaplastic and non-anaplastic revealed increased PFS for the latter (HR 4.57, CI 95% 1.32-15.7, p = 0.0164). We could not verify previous clinical parameters as prognostic factors in malignant meningioma. MI and the PHH3 MI were prognostic within WHO grade III meningiomas for PFS. An overall tumor staining of Ki-67 > 10% correlated with PFS and OS within grade III tumors.

WHO grade I meningiomas: classification-tree for prognostic factors of survival.

World Health Organization (WHO) grade I meningiomas are intracranial extracerebral tumors, in which microsurgery as a stand-alone therapy provides high rates of disease control and low recurrence rates. Our aim was to identify prognostic factors of overall survival and time-to-retreat (OS; TTR) in a cohort of patients with surgically managed WHO grade I meningioma. Patients with WHO grade I meningiomas from a retrospectively (1990 to 2002) and prospectively managed (2003 to 2010) databank of Oslo University Hospital, Norway, were included. The mean follow-up was 9.2 ± 5.7 years, with a total of 11,414 patient-years. One thousand three hundred fifty-five patients were included. The mean age was 58 ± 13.2, mean Karnofsky Performance Status (KPS) 92.6 ± 26.1 and female-to-male ratio 2.5:1. The 1-year, 5-year, 10-year, 15-year, and 20-year probabilities were 0.98, 0.91, 0.87, 0.84, and 0.8 for TTR. Patient age (OR 0.92 [0.91, 0.94]), male sex (OR 0.59 [0.45, 0.76]), preoperative KPS ≥ 70 (OR 2.22 [1.59, 3.13]), skull base location (OR 0.77 [0.60, 1]), and the occurrence of a postoperative hematoma (OR 0.44 [0.26, 0.76]) were identified as independent prognostic factors of OS. Patient age (OR 1.02 [1.01, 1.03]) and skull base location (OR 0.30 [0.21, 0.45]) were independent predictors of decreased PFS. Using a recursive partitioning analysis, we suggest a classification tree for the prediction of 5-year PFS based on patient and tumor characteristics. The findings from this cohort of meningioma WHO I patients helps to identify patients at risk of recurrence and tailor the therapeutic management.

Lateral sphenoid wing meningiomas without bone invasion-still skull base surgery?

Sphenoid wing meningiomas are generally considered as skull base meningiomas (SBMs). However, given their surgical similarities with non-skull base meningiomas (NSBMs), we hypothesized that lateral sphenoid wing meningiomas (LSWMs) without bone invasion (BI) should be considered as NSBMs. N = 65 LSWMs without BI operated between 1990 to 2010 at a single-center were compared to N = 352 NSBMs, represented by convexity meningiomas (CMs), and to N = 23 SBMs, represented by spheno-orbital meningiomas (SOMs), with respect to baseline demographics, clinical presentations, Simpson grades, complications, adjuvant therapies, as well as overall survival (OS) and progression-free survival (PFS). Only WHO grade I meningiomas were included. No significant differences in baseline demographics, clinical presentation, or pre-operative KPS were found between the three groups. Simpson grade 1-3 was achieved in 90.1% of LSWMs, 97.1% in CMs (p = 0.05), and 82.6% in SOMs (p = 0.23). There were no significant differences in postoperative infection, hematoma, neurological worsening, 30-day mortality, or OS between the three groups. Lower re-treatment rates were observed in LSWMs and CMs compared to SOMs (p = 0.06). With respect to PFS, there was no significant difference between LSWMs and CMs (89.1% and 88.5% at 5 years, respectively), whereas PFS was significantly higher in LSWMs than in SOMs (79% at 5 years) (p = 0.05). LSWMs without BI should be considered as an intermediate entity between NSBMs and SBMs. LSWMs are similar to SOMs with respect to extent of resection, but more similar to CMs with respect to re-treatment rates and PFS.