Incidence, management, and outcome of incidental meningioma: what has happened in 10 years?

PURPOSE: The aim of this study was to study the use of brain scanning, and the subsequent findings of presumed incidental meningioma in two time periods, and to study differences in follow-up, treatment, and outcome. METHODS: Records of all performed CT and MRI of the brain during two time periods were retrospectively reviewed in search of patients with presumed incidental meningioma. These patients were further analyzed using medical health records, with the purpose to study clinical handling and outcome during a 3 year follow up. RESULTS: An identical number of unique patients underwent brain imaging during the two time periods (n = 22 259 vs. 22 013). In 2018-2019, 25% more incidental meningiomas were diagnosed compared to 2008-2009 (n = 161 vs. 129, p = 0.052). MRI was used more often in 2018-2019 (26.1 vs. 12.4%, p = 0.004), and the use of contrast enhancement, irrespective of modality, also increased (26.8 vs. 12.2%, p < 0.001). In the most recent cohort, patients were older (median 79 years vs. 73 years, p = 0.03). Indications showed a significant increase of cancer without known metastases among scanned patients. 29.5 and 35.4% of patients in the cohorts were deceased 3 years after diagnosis for causes unrelated to their meningioma. CONCLUSIONS: Despite the same number of unique patients undergoing brain scans in the time periods, there was a trend towards more patients diagnosed with an incidental asymptomatic meningioma in the more recent years. This difference may be attributed to more contrast enhanced scans and more scans among the elderly but needs to be further studied. Patients in the cohort from 2018 to 2019 more often had non-metastatic cancer, with their cause of scan screening for metastases. There was no significant difference in management decision at diagnosis, but within 3 years of follow up significantly more patients in the latter cohort had been re-scanned. Almost a third of all patients were deceased within 3 years after diagnosis, due to causes other than their meningioma.

Healthcare utilization and costs among intracranial meningioma patients during long-term follow-up.

PURPOSE: Few studies have reported on healthcare utilization and costs for intracranial meningioma patients, while the tumor and its treatment profoundly affect patients' functioning and well-being. Here we evaluated healthcare utilization and costs, including their determinants. METHODS: A multicenter cross-sectional study of adult meningioma patients ≥ 5 years after intervention. Patients completed three validated patient-reported outcome measures (PROMs) assessing patients 'functioning and wellbeing (SF-36, EORTC QLQ-BN20, and HADS) and a study-specific questionnaire assessing healthcare utilization over the previous twelve months. Healthcare costs of the twelve months prior were calculated using reported healthcare utilization ≥ 5 years after intervention by the Dutch Manual for Economic Evaluation in Healthcare. Determinants for healthcare utilization and costs were determined with regression analyses. RESULTS: We included 190 patients with WHO grade I or II meningioma after a mean follow-up since intervention of 9.2 years (SD 4.0). The general practitioner (80.5%), physiotherapist (37.9%), and neurologist (25.4%) were visited most often by patients. Median annual healthcare costs were €871 (IQR €262-€1933). Main contributors to these costs were medication (45.8% of total costs, of which anti-seizure medication was utilized most [21.6%]), specialist care (17.7%), and physiotherapy (15.5%). Lower HRQoL was a significant determinant for higher healthcare utilization and costs. CONCLUSION: In patients with meningioma, medication costs constituted the largest expenditure of total healthcare costs, in particular anti-seizure medication. Particularly a lower HRQoL was a determinant for healthcare utilization and costs. A patient-specific approach aimed at improving patients' HRQoL and needs could be beneficial in reducing disease burden and functional recovery.

Efficacy of endovascular intratumoral embolization for meningioma: assessment using dynamic susceptibility contrast-enhanced perfusion-weighted imaging.

BACKGROUND: In preoperative embolization for intracranial meningioma, endovascular intratumoral embolization is considered to be more effective for the reduction of tumorous vascularity than proximal feeder occlusion. In this study, we aimed to reveal different efficacies for reducing tumor blood flow in meningiomas by comparing endovascular intratumoral embolization and proximal feeder occlusion using dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI). METHODS: 28 consecutive patients were included. DSC-PWI was performed before and after embolization for intracranial meningiomas. Normalized tumor blood volume (nTBV) of voxels of interest of whole tumors were measured from the DSC-PWI data before and after embolization. ΔnTBV% was compared between the cases that received intratumoral embolization and proximal feeder occlusion. RESULTS: ΔnTBV% in the intratumoral embolization group (42.4±29.8%) was higher than that of the proximal feeder occlusion group (15.3±14.3%, p=0.0039). We used three types of embolic materials and ΔnTBV% did not differ between treatments with or without the use of each material: 42.8±42.4% vs 28.7±20.1% for microspheres (p=0.12), 36.1±20.6% vs 28.1±41.1% for n-butyl cyanoacrylate (p=0.33), and 32.3±37.3% vs 34.1±19.0% for bare platinum coils (p=0.77). CONCLUSIONS: The flow reduction effect of intratumoral embolization was superior to that of proximal feeder occlusion in preoperative embolization for intracranial meningioma in an assessment using DSC-PWI.

Long-Term Disease Burden and Survivorship Issues After Surgery and Radiotherapy of Intracranial Meningioma Patients.

BACKGROUND: Many intracranial meningioma patients have an impaired health-related quality of life (HRQoL) and neurocognitive functioning up to 4 yr after intervention. OBJECTIVE: To assess the long-term (≥5 yr) disease burden of meningioma patients. METHODS: In this multicenter cross-sectional study, patients ≥5 yr after intervention (including active magnetic resonance imaging (MRI) surveillance) were included and assessed for HRQoL (Short-Form Health Survey 36), neurocognitive functioning (neuropsychological assessment), anxiety and depression (Hospital Anxiety and Depression Scale), and work productivity (Short Form-Health and Labour Questionnaire). Multivariable and propensity score regression analyses were used to compare patients and controls, and different treatment strategies corrected for possible confounders. Clinically relevant differences were reported. RESULTS: At a median of 9 yr follow-up after intervention, meningioma patients (n = 190) reported more limitations due to physical (difference 12.5 points, P = .008) and emotional (13.3 points, P = .002) health problems compared with controls. Patients also had an increased risk to suffer from anxiety (odds ratio [OR]: 2.6, 95% CI: 1.2-5.7) and depression (OR: 3.7, 95% CI: 1.3-10.5). Neurocognitive deficits were found in 43% of patients. Although postoperative complications, radiotherapy, and reresection were associated with worse verbal memory, attention, and executive functioning when compared to patients resected once, the only clinically relevant association was between reresection and worse attention (-2.11, 95% CI: -3.52 to -0.07). Patients of working age less often had a paid job (48%) compared with the working-age Dutch population (72%) and reported more obstacles at work compared with controls. CONCLUSION: In the long term, a large proportion of meningioma patients have impaired HRQoL, neurocognitive deficits, and high levels of anxiety or depression. Patients treated with 1 resection have the best neurocognitive functioning.

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.

Variations in screening and management practices for subsequent asymptomatic meningiomas in childhood, adolescent and young adult cancer survivors.

INTRODUCTION: Childhood, adolescent and young adult (CAYA) cancer survivors treated with cranial radiotherapy are at risk for developing subsequent meningiomas. There is insufficient evidence concerning the benefits and harms of screening for subsequent meningiomas, and uncertainty about the most appropriate clinical management of asymptomatic meningiomas. Data describing current clinical decision-making is essential to formulate surveillance recommendations. METHODS: We created an online survey to identify the current international clinical practice regarding screening for and management of subsequent asymptomatic meningiomas among CAYA cancer survivors. Fifty-nine physicians from North America and Europe with expertise relevant to meningiomas were invited to participate. RESULTS: Thirty-four physicians (58%) completed the survey. The reported number of CAYA cancer survivors that physicians are willing to screen to detect one meningioma varied widely from 0 to 750 (median 50). Physicians expressed concerns regarding harms from MRI screening, including risks of unnecessary interventions (n = 25, 73%) and overdiagnosis (n = 19, 56%). Growth pattern (n = 33, 97%), location (n = 31, 91%) and size (n = 29, 85%) were endorsed as the most important factors influencing the decision to treat asymptomatic meningiomas. A challenging location (n = 14, 52%), indolent tumor growth pattern (n = 13, 48%), and absence of symptoms (n = 12, 44%) were endorsed as the main reasons to monitor without intervention. CONCLUSIONS: There is international variation in opinions and clinical practice regarding screening for subsequent asymptomatic meningiomas among at risk CAYA cancer survivors. Decision-making regarding interventions of asymptomatic meningiomas are largely driven by clinical characteristics. These valuable insights into current clinical practice will inform surveillance guidelines for CAYA cancer survivors.

Determining the role of adjuvant radiotherapy in the management of meningioma: a Surveillance, Epidemiology, and End Results analysis.

OBJECTIVEThe aim of this study was to illustrate the demographic characteristics of meningioma patients and observe the effect of adjuvant radiation therapy on survival by using the Surveillance, Epidemiology, and End Results (SEER) database. More specifically, the authors aimed to answer the question of whether adjuvant radiotherapy following resection of atypical meningioma confers a cause-specific survival benefit. Additionally, they attempted to add to previous characterizations of the epidemiology of primary meningiomas and assess the effectiveness of the standard of care for benign and anaplastic meningiomas. They also sought to characterize the efficacy of various treatment options in atypical and anaplastic meningiomas separately since nearly all other analyses have grouped these two together despite varying treatment regimens for these behavior categories.METHODSSEER data from 1973 to 2015 were queried using appropriate ICD-O-3 codes for benign, atypical, and anaplastic meningiomas. Patient demographics, tumor characteristics, and treatment choices were analyzed. The effects of treatment were examined using a multivariate Cox proportional hazards model and Kaplan-Meier survival analysis.RESULTSA total of 57,998 patients were included in the analysis of demographic, meningioma, and treatment characteristics. Among this population, cases of unspecified WHO tumor grade were excluded in the multivariate analysis, leaving a total of 12,931 patients to examine outcomes among treatment paradigms. In benign meningiomas, gross-total resection (HR 0.289, p = 0.013) imparted a significant cause-specific survival benefit over no treatment. In anaplastic meningioma cases, adjuvant radiotherapy imparted a significant survival benefit following both subtotal (HR 0.089, p = 0.018) and gross-total (HR 0.162, p = 0.002) resection as compared to gross-total resection alone. In atypical tumors, gross-total resection plus radiotherapy did not significantly change the hazard risk (HR 1.353, p = 0.628) compared to gross-total resection alone. Similarly, it was found that adjuvant radiation did not significantly benefit survival after a subtotal resection (HR 1.440, p = 0.644).CONCLUSIONSThe results of this study demonstrate that the role of adjuvant radiotherapy, especially after the resection of atypical meningioma, remains somewhat unclear. Thus, given these results, prospective randomized clinical studies are warranted to provide clear information on the effects of adjuvant radiation in meningioma treatment.

Response assessment of meningioma: 1D, 2D, and volumetric criteria for treatment response and tumor progression.

BACKGROUND: Meningiomas are the most common primary brain tumors in adults. Due to their variable growth rates and irregular tumor shapes, response assessment in clinical trials remains challenging and no standard criteria have been defined. We evaluated 1D, 2D, and volume imaging criteria to assess whether a volumetric approach might be a superior surrogate for overall survival (OS). METHODS: In this retrospective multicenter study, we evaluated the clinical and imaging data of 93 patients with recurrent meningiomas treated with pharmacotherapy. One-dimensional (1D), 2D, and volumetric measurements of enhancing tumor on pre- and post-treatment MRI were compared at 6 and 12 months after treatment initiation. Cox proportional hazards models were used to examine the relationship between each imaging criterion and OS. RESULTS: The median age of the patient cohort is 51 years (range 12-88), with 14 World Health Organization (WHO) grade I, 53 WHO grade II, and 26 WHO grade III meningiomas. Volumetric increase of 40% and unidimensional increase by 10 mm at 6 months and 12 months provided the strongest association with overall survival (HR = 2.58 and 3.24 respectively, p<0.01). Setting a volume change threshold above 40% did not correlate with survival. The interobserver agreement of 1D, 2D, and volume criteria is only moderate (kappa = 0.49, 0.46, 0.52, respectively). None of the criteria based on tumor size reduction were associated with OS (P > 0.09). CONCLUSION: Compared with 1D (Response Evaluation Criteria In Solid Tumors 1.1) and 2D (Response Assessment in Neuro-Oncology) approaches, volumetric criteria for tumor progression has a stronger association with OS, although the differences were only modest. The interobserver variability is moderate for all 3 methods. Further validation of these findings in an independent patient cohort is needed.

Proposed response assessment and endpoints for meningioma clinical trials: report from the Response Assessment in Neuro-Oncology Working Group.

No standard criteria exist for assessing response and progression in clinical trials involving patients with meningioma, and there is no consensus on the optimal endpoints for trials currently under way. As a result, there is substantial variation in the design and response criteria of meningioma trials, making comparison between trials difficult. In addition, future trials should be designed with accepted standardized endpoints. The Response Assessment in Neuro-Oncology Meningioma Working Group is an international effort to develop standardized radiologic criteria for treatment response for meningioma clinical trials. In this proposal, we present the recommendations for response criteria and endpoints for clinical trials involving patients with meningiomas.

Assessment of Costs in Open Microsurgery and Stereotactic Radiosurgery for Intracranial Meningiomas.

OBJECTIVE: Understanding costs of microsurgical or radiosurgical treatment of intracranial meningioma may offer direction in reducing health care costs and establishing cost-effective algorithms. We used the Value Driven Outcomes database, which identifies cost drivers and tracks changes over time, to evaluate cost drivers for management of intracranial meningioma. METHODS: A single-center, retrospective cohort of patients undergoing microsurgery or radiosurgery of intracranial meningiomas from July 2011 to April 2017 was analyzed. Patient and tumor characteristics, subcategory costs, and potential cost drivers were analyzed within each treatment modality. RESULTS: Of 268 intracranial meningiomas, 198 were treated with microsurgery and 70 with stereotactic radiosurgery. Facility costs were the largest contributor to total costs for microsurgery (59.7%), whereas imaging costs were the largest contributor to stereotactic radiosurgery total costs (98.2%). Patients with non-skull base tumors had larger tumors (3.7 ± 1.9 cm vs. 2.7 ± 1.2 cm, P = 0.0001) and were more likely to undergo microsurgery (81.7% vs. 55.2%) than patients with skull base tumors. Univariate analysis suggested that American Society of Anesthesiologists status, length of stay, discharge disposition, and maximal tumor size impacted cost during microsurgery (P = 0.001), but only length of stay (P = 0.0001) and maximal tumor size (P = 0.01) were drivers of total costs on multivariate analysis. For radiosurgery, age significantly affected cost on univariate (P = 0.001) and multivariate (P = 0.003) analysis. CONCLUSIONS: Implementing protocols to reduce facility usage and imaging would mitigate total costs and improve resource utilization while maintaining high-quality patient care. Additional cost-effectiveness studies evaluating patients with true therapeutic equipoise will provide further guidance in these efforts.

World Health Organization grade III meningiomas. A retrospective study for outcome and prognostic factors assessment.

BACKGROUND: To depict the outcome of patients with WHO grade III meningioma and identify factors that may influence the survival. MATERIAL AND METHODS: Between 1989 and 2007, a retrospective search identified 43 WHO grade III meningiomas after cases exclusion. Nine patients (39.5%) had a previous history of grade I or II meningioma. The patients underwent a total of 89 surgical resections and 83.7% received radiotherapy. Median follow-up was 7.4 years. RESULTS: At the end of the study, 35 patients were deceased (81.4%). One patient died of disseminated metastatic disease of a papillary meningioma. Median overall survival was 4.1 years, 95% CI [1.9, 8.3]. Overall survival probability at 1, 5 and 10 years were respectively: 81.4%, 95% CI [70.6, 93.9], 48.8%, 95% CI [36,66.3] and, 27.5%, 95% CI [16.9, 44.9]. In univariate Cox regression, a previous surgery for WHO grade I or II meningioma (HR=2.05, 95% CI [1.03, 4.07], P=0.04) and the mitosis count (HR=0.3, 95% CI [0.12, 0.79], P=0.02) were associated with the overall survival. However, neither macroscopic gross total resection (HR=0.87, 95% CI [0.4, 1.87], P=0.71), nor radiotherapy (HR=0.75, 95% CI [0.31, 1.83], P=0.53) was associated with an increased survival. CONCLUSION: This series highlights the poor prognosis associate with the diagnosis of malignant meningioma. Patients with primary WHO grade III meningioma demonstrating less than 14 mitosis per 10 high power fields may live longer. We could not confirm the usefulness of complete resection and adjuvant radiotherapy.

Quantitative Assessment of Flow Reduction After Feeder Embolization in Meningioma by Using Pseudocontinuous Arterial Spin Labeling.

BACKGROUND: Meningioma is a hypervascular tumor of the central nervous system. Angiographic disappearance of tumor blush after preoperative feeder embolization allows qualitative, but not quantitative, assessment of flow reduction. Pseudocontinuous arterial spin labeling (PCASL), which has evolved from magnetic resonance imaging techniques, allows noninvasive measurement of cerebral blood flow (CBF) using water protons in the arterial blood flow. OBJECTIVE: We applied PCASL for assessment of blood flow in meningioma and its reduction on preoperative embolization. METHODS: Forty-one consecutive patients (11 males, 30 females) with histologically proven meningioma were evaluated by PCASL. Quantitative assessment by an absolute value of tumor blood flow (TBF) and a relative value of tumor vascular index (tVI; calculated as TBF divided by CBF) were calculated. In 8 cases, in which preoperative embolization was achieved, flow reduction rate was evaluated. RESULTS: TBF of meningiomas, 155.8 mL/100 g·min(-1) on average, was 2.6 times higher than CBF, 59.9 mL/100 g·min(-1) (P < 0.001). Patients who underwent feeder embolization showed statistically greater flow reduction rate, which was calculated as 42.7% (P < 0.05). Mean tVI before embolization was 4.1, which was reduced to 2.1 after embolization. CONCLUSION: PCASL could yield quantitative assessment of blood flow in meningioma including flow reduction rate in cases of feeder embolization.

Assessment of vasculature of meningiomas and the effects of embolization with intra-arterial MR perfusion imaging: a feasibility study.

BACKGROUND AND PURPOSE: Embolization of meningiomas has emerged as a preoperative adjuvant therapy that has proved effective in mitigating blood loss during surgical resection. Arterial supply to these tumors is typically identified by diffuse areas of parenchymal staining after selective x-ray angiograms. We investigate the benefits that selective injection of MR contrast may have in identifying vascular territories and determining the effects of embolization therapy. MATERIALS AND METHODS: Selective intra-arterial (IA) injection of dilute MR contrast media was used to assess the vascular distribution territories of meningeal tumors before and after embolization therapy. Regions of the tumor that experienced loss of signal intensity after localized contrast injections into the external and common carotid as well as vertebral arteries were used to quantify the specific vessel's volume of distribution. Assessments were made before and after embolization to reveal changes in the vascular supply of the tumor. MR findings were compared with radiographic evaluation of tumor vascular supply on the basis of conventional x-ray angiography. RESULTS: MR proved to be an excellent means to assess tissue fed by selected arteries and clearly demonstrated the treated and untreated portions of the neoplasm after therapy. In some instances, MR revealed postembolization residual enhancement of the tumor that was difficult to appreciate on x-ray angiograms. Very low contrast dose was necessary, which made repeated assessment during therapy practical. CONCLUSION: MR perfusion imaging with selective IA injection of dilute contrast can reveal the distribution territory of vessels. Changes in tumor vasculature could be detected after embolization, which reveal the volumetric fraction of the tumor affected by the therapy.

Clinicopathologic assessment and grading of embolized meningiomas: a correlative study of 64 patients.

BACKGROUND: Preoperative embolization of meningiomas is commonly performed to minimize intraoperative bleeding, thereby facilitating surgery and reducing the necessity for transfusion. However, the resulting necrosis and compensatory proliferation reportedly have hampered subsequent histologic grading. METHODS: The clinicopathologic features of 64 meningiomas embolized between 1989 and 1997 were assessed. Tumors were graded according to recently published criteria. RESULTS: A good embolization result (> 75% reduction in angiographic blush) was achieved in 52%. Histologically, embolized meningiomas showed higher frequencies of necrosis (89%), nuclear atypia (72%), macronucleoli (58%), sheeting (31%), high mitotic index (30%), and brain invasion (14%) when compared with nonembolized counterparts. Median mitotic and MIB-1 indices were slightly elevated (1.5 of 10 high-power fields and 1.6%, respectively). A significant degree of necrosis (> 10%) was found in 43% and was only roughly correlated with extent of angiographic blush reduction or embolization particle size. Histologic grade was benign in 57.8%, atypical in 40.6%, and anaplastic in 1.6%. At last follow-up, there were 13 recurrences, 11 in the atypical/anaplastic (41%) versus 2 in the benign (5%) subsets (P = 0.001). CONCLUSIONS: The authors conclude that 1) their grading scheme accurately stratifies embolized meningiomas, 2) extent of necrosis is difficult to predict using standard clinical parameters, and 3) their high incidence of atypical meningioma more likely reflects patient selection biases rather than artifacts induced by the embolization procedure.

Subselective preoperative embolization for meningiomas. A radiological and pathological assessment.

Over a 2-year period the authors have studied the effects of preoperative subselective embolization of meningiomas. Thirty-six consecutive patients shown by computerized tomography (CT) to have a meningioma underwent selective internal and external carotid artery angiography, and any significant external carotid artery feeders were embolized (27 cases). It was found that CT and dynamic radioisotope scan findings were unable to predict the degree of vascularity of the tumor or its suitability for embolization. Furthermore, these tests, repeated after embolization, were unreliable in detecting either the extent of necrosis or reduction in blood flow. The effects of embolization upon surgery were recorded, and the excised tumor specimen examined for evidence of thrombosis and infarction. Subselective embolization was determined to be a simple, safe, and effective method of producing tumor necrosis and intraoperative hemostasis in selected patients.