Regression of Intracranial Meningioma during Treatment with α1-Adrenoceptor Blocker.
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ABSTRACT:
SUBMITTER: Hoegestoel EA
PROVIDER: S-EPMC4863873 | biostudies-other | 2016 Mar
REPOSITORIES: biostudies-other
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Project description:Recurrent meningiomas remain a substantial treatment challenge given the lack of effective therapeutic options aside from surgery and radiation therapy, which yield limited results in the retreatment situation. Systemic therapies have little effect, and responses are rare; the search for effective systemic therapeutics remains elusive. In this case report, we provide data regarding significant responses in two radiographically diagnosed intracranial meningiomas in a patient with concurrent thyroid carcinoma treated with cabozantinib, an oral multitarget tyrosine kinase inhibitor with potent activity against MET and VEGF receptor 2. Given the clinical experience supporting the role of VEGF agents as experimental therapeutics in meningioma and the current understanding of the biological pathways underlying meningioma growth, this may represent a new oral therapeutic alternative, warranting prospective evaluation.
| S-EPMC8167720 | biostudies-literature
Project description:PurposeFew 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.MethodsA 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.ResultsWe 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.ConclusionIn 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.
| S-EPMC9988802 | biostudies-literature
Project description:BACKGROUND:Single session radiosurgery represents a widely accepted treatment for intracranial meningiomas. However, this approach could involve a high risk of treatment-related complications when applied to large volume lesions. In these cases and for those not suitable for surgical resection, radiosurgery in multisession setting could represents a viable option. The literature results are reassuring in terms of correlated adverse events as well as in terms of tumor control. However, no prospective long-term results are available. In this scenario, we design a prospective monocentric phase II study, in order to verify the safety of a multisession radiosurgery schedule delivering 25 Gy in 5 daily fractions. METHODS:Patients diagnosed with large and/or near to critical structures, intracranial meningiomas have been treated by means of multisession radiosurgery in both exclusive and postoperative settings. The primary study aim is safety that has been being prospectively scored based on international scales, including NCI Common Toxicity criteria, version 4.03, Barrow Neurological Institute pain intensity score, Barrow Neurological Institute facial numbness score and House-Brackmann Facial Nerve Grading System for qualitative analysis. Secondary aim is treatment efficacy in terms of local control that has been being assessed on volumetric analysis. DISCUSSION:This is the first prospective phase II trial on multisession radiosurgery for large and/or near to critical structures intracranial meningiomas. If positive results will be found, this study could represent the starting point for a phase III trial exploring the role of multisession radiosurgery in the exclusive and postoperative radiation therapy treatment of intracranial meningiomas. TRIAL REGISTRATION:Trial registration: clinicaltrials.gov platform (Multisession Radiosurgery in Large Meningiomas -MuRaLM- identifier NCT02974127). Registered: November 28, 2016. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02974127?term=radiosurgery&cond=Intracranial+Meningioma&draw=2&rank=1.
| S-EPMC6993396 | biostudies-literature
Project description:The outcomes following re-operation for meningioma are poorly described. The aim of this study was to identify risk factors for a performance status outcome following a second operation for a recurrent meningioma. A retrospective, comparative cohort study was conducted. The primary outcome measure was World Health Organization performance. Secondary outcomes were complications, and overall and progression free survival (OS and PFS respectively). Baseline clinical characteristics, tumor details, and operation details were collected. Multivariable binary logistic regression was used to identify risk factors for performance status outcome following a second operation. Between 1988 and 2018, 712 patients had surgery for intracranial meningiomas, 56 (7.9%) of which underwent a second operation for recurrence. Fifteen patients (26.8%) had worsened performance status after the second operation compared to three (5.4%) after the primary procedure (p = 0.002). An increased number of post-operative complications following the second operation was associated with a poorer performance status following that procedure (odds ratio 2.2 [95% CI 1.1-4.6]). The second operation complication rates were higher than after the first surgery (46.4%, n = 26 versus 32.1%, n = 18, p = 0.069). The median OS was 312.0 months (95% CI 257.8-366.2). The median PFS following the first operation was 35.0 months (95% CI 28.9-41.1). Following the second operation, the median PFS was 68.0 months (95% CI 49.1-86.9). The patients undergoing a second operation for meningioma had higher rates of post-operative complications, which is associated with poorer clinical outcomes. The decisions surrounding second operations must be balanced against the surgical risks and should take patient goals into consideration.
| S-EPMC8507983 | biostudies-literature
Project description:Protein kinase C (PKC) plays key roles in the regulation of signal transduction and cellular function in various cell types. At least ten PKC isoforms have been identified and intracellular localization and trafficking of these individual isoforms are important for regulation of enzyme activity and substrate specificity. PKC can be activated downstream of Gq-protein coupled receptor (GqPCR) signaling and translocate to various cellular compartments including plasma membrane (PM). Recent reports suggested that different types of GqPCRs would activate different PKC isoforms (classic, novel and atypical PKCs) with different trafficking patterns. However, the knowledge of isoform-specific activation of PKC by each GqPCR is limited. α1-Adrenoceptor (α1-AR) is one of the GqPCRs highly expressed in the cardiovascular system. In this study, we examined the isoform-specific dynamic translocation of PKC in living HEK293T cells by α1-AR stimulation (α1-ARS). Rat PKCα, βI, βII, δ, ε and ζ fused with GFP at C-term were co-transfected with human α1A-AR into HEK293T cells. The isoform-specific dynamic translocation of PKC in living HEK293T cells by α1-ARS using phenylephrine was measured by confocal microscopy. Before stimulation, GFP-PKCs were localized at cytosolic region. α1-ARS strongly and rapidly translocated a classical PKC (cPKC), PKCα, (<30 s) to PM, with PKCα returning diffusively into the cytosol within 5 min. α1-ARS rapidly translocated other cPKCs, PKCβI and PKCβII, to the PM (<30 s), with sustained membrane localization. One novel PKC (nPKC), PKCε, but not another nPKC, PKCδ, was translocated by α1-AR stimulation to the PM (<30 s) and its membrane localization was also sustained. Finally, α1-AR stimulation did not cause a diacylglycerol-insensitive atypical PKC, PKCζ translocation. Our data suggest that PKCα, β and ε activation may underlie physiological and pathophysiological responses of α1-AR signaling for the phosphorylation of membrane-associated substrates including ion-channel and transporter proteins in the cardiovascular system.
| S-EPMC4564329 | biostudies-literature
Project description:ObjectiveAnticoagulation (AC) is a critical topic in perioperative and post-bleeding management. Nevertheless, there is a lack of data about the safe, judicious use of prophylactic and therapeutic anticoagulation with regard to risk factors and the cause and modality of brain tissue damage as well as unfavorable outcomes such as postoperative hemorrhage (PH) and thromboembolic events (TE) in neurosurgical patients. We therefore present retrospective data on perioperative anticoagulation in meningioma surgery.MethodsData of 286 patients undergoing meningioma surgery between 2006 and 2018 were analyzed. We followed up on anticoagulation management, doses and time points of first application, laboratory values, and adverse events such as PH and TE. Pre-existing medication and hemostatic conditions were evaluated. The time course of patients was measured as overall survival, readmission within 30 days after surgery, as well as Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS). Statistical analysis was performed using multivariate regression.ResultsWe carried out AC with Fraxiparin and, starting in 2015, Tinzaparin in weight-adapted recommended prophylactic doses. Delayed (216 ± 228h) AC was associated with a significantly increased rate of TE (p = 0.026). Early (29 ± 21.9h) prophylactic AC, on the other hand, did not increase the risk of PH. We identified additional risk factors for PH, such as blood pressure maxima, steroid treatment, and increased white blood cell count. Patients' outcome was affected more adversely by TE than PH (+3 points in modified Rankin Scale in TE vs. +1 point in PH, p = 0.001).ConclusionEarly prophylactic AC is not associated with an increased rate of PH. The risks of TE seem to outweigh those of PH. Early postoperative prophylactic AC in patients undergoing intracranial meningioma resection should be considered.
| S-EPMC7462284 | biostudies-literature
Project description:PurposeTamsulosin has been associated with dementia, but the results have been inconsistent. Concerns have been raised about using exposure assessment time too close to the outcome. We investigated the association between use of α1-adrenoceptor antagonists indicated for benign prostate hyperplasia and risk of Alzheimer's disease (AD) using different exposure windows.MethodsThe study (24 602 cases and 98 397 matched controls) included men from the Finnish nationwide nested case-control study on Medication and Alzheimer's disease (MEDALZ). Cases received clinically verified AD diagnosis during 2005-2011 and were community-dwelling at the time of diagnosis. Use of tamsulosin and alfuzosin in 1995-2011 was identified from the Prescription Register and categorized based on whether it had occurred within 3 years before AD diagnosis (lag time) or before that. Dose-response analysis using defined daily doses of drug (DDDs) was conducted. Associations were investigated with conditional logistic regression, adjusted for confounders and mediators.ResultsThe use of α1-adrenoceptor antagonists before lag time associated with an increased risk of AD (OR 1.24 [1.20-1.27]). After adjustment for comorbidities and concomitant drug use throughout the assessment time (confounders) and healthcare contacts within the lag period (mediators), the association weakened (aOR 1.10 [1.06-1.14]). We found no evidence of dose-response-relationship when comparing the users of higher than median DDDs to the users of lower than median DDDs.ConclusionOur findings, especially the lack of dose-response-relationship and attenuation after mediator adjustment, do not provide strong support for the previous hypothesis on α1-adrenoceptor antagonists as a risk factor for dementia.
| S-EPMC9542191 | biostudies-literature
Project description:BackgroundThe availability of image guidance and intensity modulation has led to the increasing use of hypofractionated stereotactic radiotherapy (hSRT) as an alternative to conventionally fractionated radiotherapy or radiosurgery for intracranial meningiomas (ICMs). As the safety and efficacy of this approach is not well characterized, we conducted a systematic review of the literature to assess the clinical outcomes of hSRT in the setting of ICMs.MethodsA systematic review of Medline and EMBASE databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies were retrospective or prospective series that examined an ICM population of ≥10 patients, delivered >1 fraction of photon hSRT (≥2.5 Gy per fraction), and had a median follow-up of ≥2 years. Descriptive statistics were generated for included studies.ResultsOf 1480 initial studies, 14 met eligibility criteria for inclusion, reporting on 630 patients (age range, 18-90) treated for 638 tumors. Primary radiotherapy was delivered in 37% of patients, 36% had radiation following surgery, and surgical details were unavailable for 27%. In 474 tumors assessed for radiologic response, 78% remained stable, 18% decreased in size, and 4% increased in size. Crude local control was 90%-100% as reported in 10 studies. The median late toxicity rate was 10%. The most common significant late toxicities were decreased visual acuity and new cranial neuropathy.ConclusionsWith limited follow-up, the available literature suggests hSRT for ICMs has local control and toxicity profiles comparable to other radiotherapy approaches. Confirmation in larger patient cohorts with a longer duration of follow-up is required.
| S-EPMC6753355 | biostudies-literature
Project description:BackgroundRecent comprehensive studies have revealed several molecular alterations that are frequently found in meningiomas. However, effective treatment reagents targeting specific molecular alterations have not yet been identified because of the limited number of representative research models of meningiomas.MethodsWe performed organoid cultures using meningioma cells and meningioma tumor tissues. Using immunohistochemistry and molecular analyses consisting of whole-exome sequencing, RNA-seq, and DNA methylation analyses, we compared the histological findings and molecular profiling of organoid models with those of parental tumors. Further, using these organoid models together with a public database of meningiomas, we explored molecular alterations, which are a potent treatment target for meningioma.ResultsWe established 18 organoid models comprising of two malignant meningioma cells (HKBMM and IOMM-Lee), 10 benign meningiomas, four malignant meningiomas, and two solitary fibrous tumors (SFTs). The organoids exhibited consistent histological features and molecular profiles with those of the parental tumors. Using a public database, we identified that upregulated forkhead box M1 (FOXM1) was correlated with increased tumor proliferation. Overexpression of FOXM1 in benign meningioma organoids increased organoid proliferation; depletion of FOXM1 in malignant organoids decreased proliferation. Additionally, thiostrepton, a FOXM1 inhibitor combined with radiation therapy, significantly inhibited the proliferation of malignant meningioma organoid models.ConclusionsAn organoid model for meningioma enabled us to elucidate the tumor biology of meningioma along with potent treatment targets for meningioma.
| S-EPMC8563327 | biostudies-literature
Project description:Surgical resection is the main therapeutic option for intracranial meningiomas, but it is not without significant morbidities. The Surgical Apgar Score (SAS), assessed by intraoperative blood pressure, heart rate, and blood loss, was developed for prognostic prediction in general and vascular surgery. We aimed to examine whether the application of SAS in patients undergoing craniotomy for meningioma resection can predict postoperative major complications. We retrospectively enrolled 99 patients that had undergone intracranial meningioma surgery. The patients were subdivided into 2 groups based on whether major complications were present (N = 34) or not (N = 65). We recognized the intergroup differences in SAS and clinical variables. The incidence of 30-day major complications in patients after operation was 34.3%. The lengths of ICU and hospital stay for the morbid cases were prolonged significantly (p = 0.009, p < 0.001, respectively). In the multivariate logistic regression model, SAS was an independent predicting factor of major complications following surgery for intracranial meningiomas (odds ratio, 95% confidence interval = 0.57, 0.38-0.87; p = 0.009), and thus a decrease of one mean SAS increased the rate of major complications by 43%. In conclusions, SAS is an independent predictor of major complications in patients undergoing intracranial meningioma surgery, and provides acceptable risk discrimination. Since this scoring system is relatively simple, objective, and practical, we suggest that SAS be included as an indicator in the guidance for the level of care after craniotomy for meningioma resection.
| S-EPMC5383036 | biostudies-literature