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

The prevalence and severity of fatigue in meningioma patients and its association with patient-, tumor-and treatment-related factors

Background: Fatigue is a commonly reported and severe symptom in primary brain tumor patients, but the exact occurrence in meningioma patients is unknown. This study aimed to determine the frequency and severity of fatigue in meningioma patients as well as associations between the level of fatigue and patient-, tumor-, and treatment-related factors. Methods: In this multicenter cross-sectional study, meningioma patients completed questionnaires on fatigue (MFI-20), sleep (PSQI), anxiety and depression (HADS), tumor-related symptoms (MDASI-BT), and cognitive functioning (MOS-CFS). Multivariable regression models were used to evaluate the independent association between fatigue and each patient-, tumor-, and treatment-related factor separately, corrected for relevant confounders. Results: Based on predetermined in-and exclusion criteria, 275 patients, on average 5.3 (SDa=a2.0) year since diagnosis, were recruited. Most patients had undergone resection (92%). Meningioma patients reported higher scores on all fatigue subscales compared to normative data and 26% were classified as fatigued. Having experienced a complication due to resection (OR 3.6, 95% CI: 1.8-7.0), having received radiotherapy (OR 2.4, 95% CI: 1.2-4.8), a higher number of comorbidities (OR 1.6, 95% CI: 1.3-1.9) and lower educational level (low level as reference; high level OR 0.3, 95% CI: 0.2-0.7) were independently associated with more fatigue. Conclusions: Fatigue is a frequent problem in meningioma patients even many years after treatment. Both patient-and treatment-related factors were determinants of fatigue, with the treatment-related factors being the most likely target for intervention in this patient population.</p

The endoscope-assisted supraorbital “keyhole” approach for anterior skull base meningiomas: an updated meta-analysis

Abstract: Introduction: The gold-standard treatment for symptomatic anterior skull base meningiomas is surgical resection. The endoscope-assisted supraorbital “keyhole” approach (eSKA) is a promising technique for surgical resection of olfactory groove (OGM) and tuberculum sellae meningioma (TSM) but has yet to be compared with the microscopic transcranial (mTCA) and the expanded endoscopic endonasal approach (EEA) in the context of existing literature. Methods: An updated study-level meta-analysis on surgical outcomes and complications of OGM and TSM operated with the eSKA, mTCA, and EEA was conducted using random-effect models. Results: A total of 2285 articles were screened, yielding 96 studies (2191 TSM and 1510 OGM patients). In terms of effectiveness, gross total resection incidence was highest in mTCA (89.6% TSM, 91.1% OGM), followed by eSKA (85.2% TSM, 84.9% OGM) and EEA (83.9% TSM, 82.8% OGM). Additionally, the EEA group had the highest incidence of visual improvement (81.9% TSM, 54.6% OGM), followed by eSKA (65.9% TSM, 52.9% OGM) and mTCA (63.9% TSM, 45.7% OGM). However, in terms of safety, the EEA possessed the highest cerebrospinal fluid leak incidence (9.2% TSM, 14.5% OGM), compared with eSKA (2.1% TSM, 1.6% OGM) and mTCA (1.6% TSM, 6.5% OGM). Finally, mortality and intraoperative arterial injury were 1% or lower across all subgroups. Conclusions: In the context of diverse study populations, the eSKA appeared not to be associated with increased adverse outcomes when compared with mTCA and EEA and offered comparable effectiveness. Case-selection is paramount in establishing a role for the eSKA in anterior skull base tumours

Public perspectives on protective measures during the COVID-19 pandemic in the Netherlands, Germany and Italy: A survey study

Background: The extent to which people implement government-issued protective measures is critical in preventing further spread of coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2. Our study aimed to describe the public belief in the effectiveness of protective measures, the reported implementation of these measures, and to identify communication channels used to acquire information on COVID-19 in European countries during the early stage of the pandemic. Methods and findings: An online survey available in multiple languages was disseminated starting on March 19th, 2020. After five days, we computed descriptive statistics for countries with more than 500 respondents. Each day, we assessed enacted community containment measures by stage of stringency (I-IV). In total, 9,796 adults responded, of whom 8,611 resided in the Netherlands (stage III), 604 in Germany (stage III), and 581 in Italy (stage IV). To explore possible dynamics as containment strategies intensified, we also included 1,365 responses submitted during the following week. Participants indicated support for governmental measures related to avoiding social gatherings, selective closure of public places, and hand hygiene and respiratory measures (range for all measures: 95.0%-99.7%). Respondents from the Netherlands less frequently considered a complete social lockdown effective (59.2%), compared to respondents in Germany (76.6%) or Italy (87.2%). Italian residents applied enforced social distancing measures more frequently (range: 90.2%-99.3%, German and Dutch residents: 67.5%-97.0%) and self-initiated hygienic and social distancing behaviors (range: 36.3%-96.6%, German and Dutch residents: 28.3%-95.7%). Respondents reported being sufficiently informed about the outbreak and behaviors to avoid infection (range: 90.2%-91.1%). Information channels most commonly reported included television newspapers, official health websites, and social media. One week later, we observed no major differences in submitted responses. Conclusions: During the early stage of the COVID-19 pandemic, belief in the effectiveness of protective measures among survey respondents from three European countries was high and participants reported feeling sufficiently informed. In March 2020, implementation of measures differed between countries and were highest among respondents from Italy, who were subjected to the most stringent lockdown measures and greatest COVID-19 burden in Europe during this period

Skull base repair following endonasal pituitary and skull base tumour resection: a systematic review.

PURPOSE: Postoperative cerebrospinal fluid rhinorrhoea (CSFR) remains a frequent complication of endonasal approaches to pituitary and skull base tumours. Watertight skull base reconstruction is important in preventing CSFR. We sought to systematically review the current literature of available skull base repair techniques. METHODS: Pubmed and Embase databases were searched for studies (2000-2020) that (a) reported on the endonasal resection of pituitary and skull base tumours, (b) focussed on skull base repair techniques and/or postoperative CSFR risk factors, and (c) included CSFR data. Roles, advantages and disadvantages of each repair method were detailed. Random-effects meta-analyses were performed where possible. RESULTS: 193 studies were included. Repair methods were categorised based on function and anatomical level. There was absolute heterogeneity in repair methods used, with no independent studies sharing the same repair protocol. Techniques most commonly used for low CSFR risk cases were fat grafts, fascia lata grafts and synthetic grafts. For cases with higher CSFR risk, multilayer regimes were utilized with vascularized flaps, gasket sealing and lumbar drains. Lumbar drain use for high CSFR risk cases was supported by a randomised study (Oxford CEBM: Grade B recommendation), but otherwise there was limited high-level evidence. Pooled CSFR incidence by approach was 3.7% (CI 3-4.5%) for transsphenoidal, 9% (CI 7.2-11.3%) for expanded endonasal, and 5.3% (CI 3.4-7%) for studies describing both. Further meaningful meta-analyses of repair methods were not performed due to significant repair protocol heterogeneity. CONCLUSIONS: Modern reconstructive protocols are heterogeneous and there is limited evidence to suggest the optimal repair technique after pituitary and skull base tumour resection. Further studies are needed to guide practice

The endoscopic endonasal approach is not superior to the microscopic transcranial approach for anterior skull base meningiomas—a meta-analysis

Object In the past decade, the endonasal transsphenoidal approach (eTSA) has become an alternative to the microsurgical transcranial approach (mTCA) for tuberculum sellae meningiomas (TSMs) and olfactory groove meningiomas (OGMs). The aim of this meta-analysis was to evaluate which approach offered the best surgical outcomes. Methods: A systematic review of the literature from 2004 and meta-analysis were conducted in accordance with the PRISMA guidelines. Pooled incidence was calculated for gross total resection (GTR), visual improvement, cerebrospinal fluid (CSF) leak, intraoperative arterial injury, and mortality, comparing eTSA and mTCA, with p-interaction values. Results: Of 1684 studies, 64 case series were included in the meta-analysis. Using the fixed-effects model, the GTR rate was significantly higher among mTCA patients for OGM (eTSA: 70.9% vs. mTCA: 88.5%, p-interaction < 0.01), but not significantly higher for TSM (eTSA: 83.0% vs. mTCA: 85.8%, p-interaction = 0.34). Despite considerable heterogeneity, visual improvement was higher for eTSA than mTCA for TSM (p-interaction < 0.01), but not for OGM (p-interaction = 0.33). CSF leak was significantly higher among eTSA patients for both OGM (eTSA: 25.1% vs. mTCA: 10.5%, p-interaction < 0.01) and TSM (eTSA: 19.3%, vs. mTCA: 5.81%, p-interaction < 0.01). Intraoperative arterial injury was higher among eTSA (4.89%) than mTCA patients (1.86%) for TSM (p-interaction = 0.03), but not for OGM resection (p-interaction = 0.10). Mortality was not significantly different between eTSA and mTCA patients for both TSM (p-interaction = 0.14) and OGM resection (p-interaction = 0.88). Random-effect models yielded similar results. Conclusion: In this meta-analysis, eTSA was not shown to be superior to mTCA for resection of both OGMs and TSMs. Electronic supplementary material The online version of this article (10.1007/s00701-017-3390-y) contains supplementary material, which is available to authorized users

Visual outcomes after endoscopic endonasal pituitary adenoma resection: a systematic review and meta-analysis

Purpose Patients with pituitary adenomas often present with visual deficits. While the aim of endoscopic endonasal transsphenoidal surgery (EETS) is to improve these deficits, permanent worsening is a possible outcome. The aim of this meta-analysis was to evaluate the effect of EETS for pituitary adenomas on visual outcomes. Methods: A meta-analysis was conducted according to the PRISMA guidelines. Pooled prevalence was calculated for complete recovery, improvement, and deterioration of visual field deficits, visual acuity and unspecified visual function in fixed- and random-effect models, including assessment of heterogeneity (I2) and publication bias (Begg’s test). Results: Out of 2636 articles, 35 case series were included in the meta-analysis. Results are described for fixed-effect models. For patients with impaired visual acuity, only one study reported complete recovery (27.2%). Pooled prevalence for improvement was 67.5% (95% CI = 59.1–75.0%), but with considerable heterogeneity (I2: 86.0%), and 4.50% (95% CI = 1.80–10.8%) for patients experiencing deterioration. For patients with visual field deficits, the prevalence was 40.4% (95% CI = 34.8–46.3%) for complete recovery, 80.8% (95% CI = 77.7–83.6%) for improvement, and 2.3% (95% CI = 1.1–4.7%) for deterioration. For the unspecified visual outcomes, pooled prevalence of complete recovery was 32.9% (95% CI: 28.5–37.7%), but with considerable heterogeneity (I2 = 84.2%). The prevalence was 80.9% (95% CI = 77.9–83.6) for improvement and 2.00% (95% CI = 1.10–3.40%) for deterioration. Random-effect models yielded similar results. Publication bias was non-significant for all the outcomes. Conclusion: While visual deficits improved after EETS in the majority of patients, complete recovery was only achieved in less than half of the patients and some patients even suffered from visual deterioration. Electronic supplementary material The online version of this article (doi:10.1007/s11102-017-0815-9) contains supplementary material, which is available to authorized users

The outcomes measured and reported in intracranial meningioma clinical trials: A systematic review

Background Meningioma clinical trials have assessed interventions including surgery, radiotherapy, and pharmacotherapy. However, agreement does not exist on what, how, and when outcomes of interest should be measured. To do so would allow comparative analysis of similar trials. This systematic review aimed to summarize the outcomes measured and reported in meningioma clinical trials. Methods Systematic literature and trial registry searches were performed to identify published and ongoing intracranial meningioma clinical trials (PubMed, Embase, Medline, CINAHL via EBSCO, and Web of Science, completed January 22, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were deduplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the “Core Outcome Measures in Effectiveness Trials” (COMET) initiative. Results Thirty published articles and 18 ongoing studies were included, describing 47 unique clinical trials: Phase 2 n = 33, phase 3 n = 14. Common interventions included: Surgery n = 13, radiotherapy n = 8, and pharmacotherapy n = 20. In total, 659 verbatim outcomes were reported, of which 84 were defined. Following de-duplication, 415 unique verbatim outcomes remained and were grouped into 115 standardized outcome terms. These were classified using the COMET taxonomy into 29 outcome domains and 5 core areas. Conclusions Outcome measurement across meningioma clinical trials is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a core outcome set for use in future meningioma clinical trials

The outcomes measured and reported in observational studies of incidental and untreated intracranial meningioma: A systematic review

Background The clinical management of patients with incidental intracranial meningioma varies markedly and is often based on clinician choice and observational data. Heterogeneous outcome measurement has likely hampered knowledge progress by preventing comparative analysis of similar cohorts of patients. This systematic review aimed to summarize the outcomes measured and reported in observational studies. Methods A systematic literature search was performed to identify published full texts describing active monitoring of adult cohorts with incidental and untreated intracranial meningioma (PubMed, EMBASE, MEDLINE, and CINAHL via EBSCO, completed January 24, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were de-duplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the “Core Outcome Measures in Effectiveness Trials” (COMET) initiative. Results Thirty-three published articles and 1 ongoing study were included describing 32 unique studies: study designs were retrospective n = 27 and prospective n = 5. In total, 268 verbatim outcomes were reported, of which 77 were defined. Following de-duplication, 178 unique verbatim outcomes remained and were grouped into 53 standardized outcome terms. These were classified using the COMET taxonomy into 9 outcome domains and 3 core areas. Conclusions Outcome measurement across observational studies of incidental and untreated intracranial meningioma is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a Core Outcome Set for use in future observational studies

Starting point for benchmarking outcomes and reporting of pituitary adenoma surgery within the European Reference Network on Rare Endocrine Conditions (Endo-ERN): results from a meta-analysis and survey study

Objective: The European Reference Network on Rare Endocrine Conditions (Endo-ERN) aims to organize high-quality healthcare throughout Europe, inc luding care for pituitary adenoma patients. As surgery is the mainstay of treatment, we aimed to describe the current surgical practice and published surgical outcomes of pi tuitary adenoma within Endo-ERN. Design and Methods: Systematic review and meta-analysis of studies reporting surgical outcomes of pituitary adenoma patients within Endo-ERN MTG6 pituitary reference centers between 2010 and 2019. A survey was completed by refere nce centers on their current surgical practice. Results: A total of 18 out of 43 (42%) reference centers located in 7 of the 20 (35%) MTG6- represented countries published 48 articles. Remission rates we re 50% (95% CI: 42–59) for patients with acromegaly, 68% (95% CI: 60–75) for Cushing’s disease, and 53% (95% CI: 39–66%) for prolactinoma. Gross total resection was achieved in 49% (95% CI: 37–61%) of patients and visual improvement in 78% (95% CI: 68–87). Mort ality, hemorrhage, and carotid injury occurred in less than 1% of patients. New-onset hypopituitarism occurred in 16% (95% CI: 11–23), transient diabetes insipidus in 12% (95 % CI: 6–21), permanent diabetes insipidus in 4% (95% CI: 3–6), syndrome of inappropria te secretion of antidiuretic hormone (SIADH) in 9% (95% CI: 5–14), severe epist axis in 2% (95% CI: 0–4), and cerebrospinal fluid leak in 4% (95% CI: 2–6). Thirty-five (81 %) centers completed the survey: 54% were operated endoscopically and 57% were together with an ENT surgeon. Conclusion: The results of this study could be used as a first benchmark for the outcomes of pituitary adenoma surgery within Endo-ERN. However, the hete rogeneity between studies in the reporting of outcomes hampers comparability and warrants outcome collection through registries