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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.
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Bases de Datos Factuales , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/epidemiología , Meningioma/mortalidad , Meningioma/patología , Anciano , Masculino , Persona de Mediana Edad , Femenino , Anciano de 80 o más Años , Neoplasias Meníngeas/epidemiología , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/patología , Estados Unidos/epidemiología , Factores de Edad , Clasificación del TumorRESUMEN
PURPOSE: To report the outcomes of a large series of intracranial meningiomas (IMs) submitted to proton therapy (PT) with curative intent. METHODS: We conducted a retrospective analysis on all consecutive IM patients treated between 2014 and 2021. The median PT prescription dose was 55.8 Gy relative biological effectiveness (RBE) and 66 GyRBE for benign/radiologically diagnosed and atypical/anaplastic IMs, respectively. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), overall survival (OS), and radionecrosis-free survival (RNFS) were evaluated with the Kaplan-Meier method. Univariable analysis was performed to identify potential prognostic factors for clinical outcomes. Toxicity was reported according to the latest Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Overall, 167 patients were included. With a median follow-up of 41 months (range, 6-99), twelve patients (7%) developed tumor local recurrence after a median time of 39 months. The 5-year LRFS was 88% for the entire cohort, with a significant difference between benign/radiologically diagnosed and atypical/anaplastic IMs (98% vs. 47%, p < 0.001); this significant difference was maintained also for the 5-year OS and the 5-year DRFS rates. Patients aged ≤ 56 years reported significantly better outcomes, whereas lower prescription doses and skull base location were associated with better RNFS rates. Two patients experienced G3 acute toxicities (1.2%), and three patients G3 late toxicities (1.8%). There were no G4-G5 adverse events. CONCLUSION: PT proved to be effective with an acceptable toxicity profile. To the best of our knowledge this is one of the largest series including IM patients submitted to PT.
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Neoplasias Meníngeas , Meningioma , Terapia de Protones , Humanos , Meningioma/radioterapia , Meningioma/mortalidad , Meningioma/patología , Estudios Retrospectivos , Femenino , Masculino , Terapia de Protones/efectos adversos , Terapia de Protones/métodos , Persona de Mediana Edad , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Adulto Joven , Estudios de Seguimiento , Resultado del Tratamiento , Tasa de Supervivencia , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/patología , PronósticoRESUMEN
OBJECTIVES: To find predictive biomarkers for recurrence and progression of meningioma. BACKGROUND: Despite great advances in meningioma treatment, the prognosis remained unfavorable due to the high recurrence rate. METHODS: In this study, we evaluated the immunohistochemical expression of FOXM1, MMP-9, and Ki67 in 50 cases of intracranial meningioma to detect its potential role in meningioma progression, recurrence, and patients' survival. RESULTS: Strong FOXM1 expression was detected in 20% of the cases and was significantly associated with meningioma grade ( P = 0.002) and peritumoral brain edema (PTBE; P <0.001). Strong MMP-9 expression was noted in 32% of the cases and was significantly associated with meningioma grade and PTBE ( P <0.001, P <0.001, respectively). High Ki67 was noted in 50% and significantly associated with tumor grade and PTBE ( P <0.001, P = 0.002, respectively). The follow-up period revealed that meningiomas with strong FOXM1, strong MMP-9, and high Ki67 expression were associated with tumor recurrence, shorter OS, and recurrence-free survival. Furthermore, up-regulation of FOXM1 and MMP-9 expression had a significant relation with poor clinical response to the therapy ( P = 0.010, P = 0. 001, respectively). However, high Ki67 cases were more sensitive to clinical therapy ( P = 0.005). CONCLUSION: Strong FOXM1, strong MMP-9, and high Ki67 in meningiomas indicate highly aggressive tumors with a shortened survival rate, dismal outcome, and high risk of recurrence after the standard protocol of therapy.
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Proteína Forkhead Box M1 , Inmunohistoquímica , Metaloproteinasa 9 de la Matriz , Meningioma , Humanos , Proteína Forkhead Box M1/metabolismo , Meningioma/metabolismo , Meningioma/patología , Meningioma/mortalidad , Femenino , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Adulto , Anciano , Clasificación del Tumor , Biomarcadores de Tumor/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/metabolismo , Regulación Neoplásica de la Expresión GénicaRESUMEN
AIMS: WHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years. MATERIALS AND METHODS: Patients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival. RESULTS: 84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection. Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27-1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27-0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy-60Gy), 45.8% of adjuvant RT was delivered using IMRT. At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT. CONCLUSION: Surgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context.
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Neoplasias Meníngeas , Meningioma , Humanos , Estudios Retrospectivos , Masculino , Femenino , Meningioma/radioterapia , Meningioma/patología , Meningioma/mortalidad , Meningioma/terapia , Meningioma/cirugía , Persona de Mediana Edad , Reino Unido , Anciano , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/terapia , Neoplasias Meníngeas/cirugía , Radioterapia Adyuvante , Adulto , Clasificación del Tumor , Anciano de 80 o más Años , Recurrencia Local de Neoplasia/radioterapiaRESUMEN
PURPOSE: This study aimed to examine the effect of postoperative radiotherapy on survival outcomes in patients with malignant meningiomas. METHODS: We identified patients with malignant meningioma diagnosed between 2007 and 2018 using the Taiwan Cancer Registry and followed them up using the death registry. Survival was compared between patients with and without adjuvant radiotherapy. The potential confounding factors evaluated in this study included age, sex, comorbidities, and the Charlson Comorbidity Index (CCI). RESULTS: The analysis included 204 patients; 94 (46%) received adjuvant radiotherapy. The two groups had similar sex distributions (p = 0.53), mean age (p = 0.33), histologic subtype (p = 0.13), and CCI (p = 0.62). The prognosis of malignant meningioma was poor, with a median overall survival (OS) of 2.4 years. The median OS was 3.0 years (interquartile range (IQR) [1.4-6.1], and 2.0 years (IQR [0.5-3.9]) in the radiotherapy and non-radiotherapy groups, respectively (p = 0.001). However, Kaplan-Meier curves with the log-rank test showed no significant difference in OS between the two groups (p = 0.999). Controlling for age group, sex, histologic subtype, treatment, comorbidities, and CCI, adjuvant radiotherapy did not impart a survival benefit (hazard ratio [HR] = 0.87; 95% confidence interval [CI]: 0.6â1.26); however, only factor of higher comorbidity score (HR = 2.03, 95%CI: 1.04â3.94) was associated with unfavorable survival. CONCLUSION: This population-based retrospective analysis suggests that the role of radiotherapy remains unclear and underscores the need for randomized clinical trials to assess the usefulness of adjuvant radiotherapy in malignant meningioma.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/radioterapia , Meningioma/mortalidad , Meningioma/patología , Meningioma/cirugía , Masculino , Femenino , Radioterapia Adyuvante , Persona de Mediana Edad , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/cirugía , Anciano , Taiwán/epidemiología , Tasa de Supervivencia , Bases de Datos Factuales , Adulto , Pronóstico , Estudios Retrospectivos , Sistema de Registros/estadística & datos numéricos , Estudios de SeguimientoRESUMEN
Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results. Currently, no reliable biomarkers are available to predict the survival, recurrence, and progression of meningioma patients in clinical practice. This study aims to evaluate the prognostic value of immunohistochemistry-based (IHC) biomarkers of meningioma patients. A systematic literature search was conducted up to November 2023 on PubMed, CENTRAL, CINAHL Plus, and Scopus databases. Two authors independently reviewed the identified relevant studies, extracted data, and assessed the risk of bias of the studies included. Meta-analyses were performed with the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). The risk of bias in the included studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool. A total of 100 studies with 16,745 patients were included in this review. As the promising markers to predict OS of meningioma patients, Ki-67/MIB-1 (HR = 1.03, 95%CI 1.02 to 1.05) was identified to associate with poor prognosis of the patients. Overexpression of cyclin A (HR = 4.91, 95%CI 1.38 to 17.44), topoisomerase II α (TOP2A) (HR = 4.90, 95%CI 2.96 to 8.12), p53 (HR = 2.40, 95%CI 1.73 to 3.34), vascular endothelial growth factor (VEGF) (HR = 1.61, 95%CI 1.36 to 1.90), and Ki-67 (HR = 1.33, 95%CI 1.21 to 1.46), were identified also as unfavorable prognostic biomarkers for poor RFS of meningioma patients. Conversely, positive progesterone receptor (PR) and p21 staining were associated with longer RFS and are considered biomarkers of favorable prognosis of meningioma patients (HR = 0.60, 95% CI 0.41 to 0.88 and HR = 1.89, 95%CI 1.11 to 3.20). Additionally, high expression of Ki-67 was identified as a prognosis biomarker for poor PFS of meningioma patients (HR = 1.02, 95%CI 1.00 to 1.04). Although only in single studies, KPNA2, CDK6, Cox-2, MCM7 and PCNA are proposed as additional markers with high expression that are related with poor prognosis of meningioma patients. In conclusion, the results of the meta-analysis demonstrated that PR, cyclin A, TOP2A, p21, p53, VEGF and Ki-67 are either positively or negatively associated with survival of meningioma patients and might be useful biomarkers to assess the prognosis.
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Biomarcadores de Tumor , Neoplasias Meníngeas , Meningioma , Meningioma/metabolismo , Meningioma/patología , Meningioma/mortalidad , Meningioma/diagnóstico , Humanos , Biomarcadores de Tumor/metabolismo , Pronóstico , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/diagnóstico , ADN-Topoisomerasas de Tipo II/metabolismo , Antígeno Ki-67/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Inmunohistoquímica , Proteínas de Unión a Poli-ADP-RibosaRESUMEN
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.
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Fragilidad , Mortalidad Hospitalaria , Neoplasias Meníngeas , Meningioma , Alta del Paciente , Humanos , Femenino , Masculino , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Fragilidad/complicaciones , Fragilidad/mortalidad , Meningioma/cirugía , Meningioma/mortalidad , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/mortalidad , Anciano , Medición de Riesgo/métodos , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Procedimientos Neuroquirúrgicos/mortalidad , Procedimientos Neuroquirúrgicos/efectos adversos , Pronóstico , Adulto , Estudios RetrospectivosRESUMEN
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.
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Bases de Datos Factuales , Neoplasias Meníngeas , Meningioma , Humanos , Femenino , Masculino , Meningioma/cirugía , Meningioma/mortalidad , Meningioma/epidemiología , Meningioma/terapia , Meningioma/patología , Niño , Adolescente , Preescolar , Lactante , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/terapia , Neoplasias Meníngeas/epidemiología , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/patología , Adulto Joven , Estudios Retrospectivos , Recién Nacido , Estudios de Cohortes , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities. MATERIALS AND METHODS: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/ß = 2 for brain tissue and α/ß = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis. RESULTS: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively). CONCLUSIONS: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice.
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Neoplasias Meníngeas , Meningioma , Recurrencia Local de Neoplasia , Reirradiación , Humanos , Meningioma/radioterapia , Meningioma/patología , Meningioma/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Reirradiación/métodos , Reirradiación/efectos adversos , Recurrencia Local de Neoplasia/radioterapia , Adulto , Anciano de 80 o más Años , Pronóstico , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/mortalidad , Adulto Joven , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
BACKGROUND: Giant meningiomas may show special features in terms of biological behavior and management. We aimed to research recurrence and mortality of giant meningiomas. METHODS: Medical files of patients with meningioma with at least 1 dimension of ≥5 cm in any plane in radiological investigations between December 2012 and January 2022 were retrospectively reviewed. Tumor dimensions were measured on magnetic resonance images except 1. All patients except two underwent clinical follow-up at a mean of 27.19 ± 29.87 (range, 4-112) months. RESULTS: There were 42 patients, 26 (61.9%) women and 16 (38.1%) men who ranged in age from 31 to 85 (mean, 60.31 ± 14.86) years. Headache (57.1%) was the most common symptom. The mean tumor size was 70.14 ± 19.03 (range, 50-152) mm. Tumors were most located at the frontal convexity (40.5%). Simpson grade I resection was achieved in 19% of the cases. The tumors were World Health Organization grade 1 in 74% and grade 2 in 26% of the cases. Major complications developed in 26.1% of the patients. Recurrence happened in 5 (11.9%) cases. The number of World Health Organization grade 2 tumors (P = 0.013; P < 0.05) and tumor size (P = 0.006; P < 0.01) were significantly higher in the recurrent cases. Mortality was % 11.9 and statistically significantly higher in the recurrence group (P = 0.025; P < 0.05). CONCLUSIONS: Giant intracranial meningiomas are challenging because of surgical experience, tumor size, peritumoral edema, blood supply, anatomical changes, and limited visibility. They have a high risk of recurrence and mortality.
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Neoplasias Meníngeas , Meningioma , Recurrencia Local de Neoplasia , Humanos , Meningioma/mortalidad , Meningioma/cirugía , Meningioma/diagnóstico por imagen , Meningioma/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/diagnóstico por imagen , Adulto , Anciano de 80 o más Años , Estudios Retrospectivos , Estudios de Cohortes , Imagen por Resonancia Magnética , Estudios de SeguimientoRESUMEN
BACKGROUND: Meningiomas are the most frequent primary intracranial tumor. While histological grade and grade of excision are established predictors of recurrence, the predictive ability of other clinical features, such as the role of radical excision of dural attachment and postoperative radiation therapy in intermediate-risk groups, remains unknown. METHODS: Clinical and radiological features and surgical details were analyzed in 451 World Health Organization (WHO) grade 1 intracranial meningiomas and 248 WHO grade 2 meningiomas operated on between 2010 and 2015. Outcomes were assessed in 352 WHO grade 1 and 208 WHO grade 2 meningiomas, studying the effect of extent of resection and use of radiation therapy. Kaplan-Meier analysis was used to determine differences in survival by extent of resection and use of postoperative radiation therapy in the treatment of the meningiomas. RESULTS: The mean age of the cohort was 46.3 years, with a female predominance. On univariate analysis, sex, WHO grade, and Simpson grade were significant predictors of recurrence. On multivariate analysis, WHO grade and Simpson grade remained significant predictors of recurrence. Recurrence was significantly associated with poor performance status and mortality. Postoperative radiation significantly improved progression-free survival among patients with grade 2 meningiomas who underwent gross total resection, but not among patients with grade 1 and grade 2 meningiomas who underwent subtotal resection. CONCLUSIONS: WHO grade and Simpson grade are independent predictors of recurrence in meningiomas. Regardless of WHO grade, gross total resection must be performed when possible, and postoperative radiation therapy may be recommended in grade 2 meningiomas.
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Neoplasias Meníngeas , Meningioma , Clasificación del Tumor , Recurrencia Local de Neoplasia , Organización Mundial de la Salud , Humanos , Meningioma/cirugía , Meningioma/patología , Meningioma/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/mortalidad , Pronóstico , Adulto , Anciano , Resultado del Tratamiento , Estudios Retrospectivos , Adulto Joven , Adolescente , Procedimientos Neuroquirúrgicos/métodos , Estimación de Kaplan-Meier , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: Psammomatous meningiomas (PMs) are a rare histological subtype of meningioma but are rather frequent in spinal meningiomas. The authors aimed to analyze the incidence, clinical features, molecular alterations, long-term outcomes, and prognostic factors of PMs. METHODS: In total, 151 patients with PMs were included in this study. Clinical characteristics, molecular alterations, and progression-free survival (PFS) were analyzed in PMs. Clinical characteristics were compared between PMs and other WHO grade 1 meningiomas. Targeted sequencing of meningioma-relevant genes was performed to determine the molecular alterations in PMs. RESULTS: PMs accounted for 1.34% of all meningiomas. Clinically, spinal location (p < 0.001) and female predominance (p < 0.001) were statistically significant in PMs when compared with the other grade 1 subtypes. Radiologically, calcification was frequently found in PMs (88.24%). Genetically, NF2 was the most frequently mutated gene in PMs (59.7%), followed by TRAF7 and AKT1. Ten patients experienced recurrence during the long-term follow-up. Multivariate analysis demonstrated that age (p = 0.009), extent of resection (p < 0.001), Ki-67 index (p = 0.007), and NF2 status (p < 0.001) were independent prognostic factors in the cohort of PMs. Interestingly, NF2 mutation was detected in all (48/48) spinal PMs (SPMs) but in only 38.46% (35/91) of cranial PMs (CPMs), revealing a significant difference (p < 0.001). The mean Ki-67 index (p = 0.044) and proportion of PMs with PR-positive expression (p = 0.048) were significantly higher in SPMs than in CPMs. The frequent NF2 mutations are associated with spinal location predominance and worse PFS in PMs. CONCLUSIONS: Female sex and spinal location predominance were statistically significant in PMs. NF2 mutation was an independent predictor for worse PFS of PMs. Of note, NF2 mutation was detected in all SPMs but in only 38.46% of CPMs, revealing a significant difference.
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Neoplasias Meníngeas , Meningioma , Mutación , Neurofibromina 2 , Humanos , Meningioma/genética , Meningioma/patología , Meningioma/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Adulto , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/mortalidad , Neurofibromina 2/genética , Anciano , Pronóstico , Péptidos y Proteínas Asociados a Receptores de Factores de Necrosis Tumoral/genética , Adulto Joven , Supervivencia sin Progresión , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/epidemiología , Proteínas Proto-Oncogénicas c-aktRESUMEN
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.
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Antineoplásicos/uso terapéutico , Furanos/uso terapéutico , Cetonas/uso terapéutico , Neoplasias Meníngeas/tratamiento farmacológico , Meningioma/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Furanos/farmacología , Humanos , Estimación de Kaplan-Meier , Cetonas/farmacología , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/patología , Meningioma/genética , Meningioma/mortalidad , Meningioma/patología , Ratones , Mutación , Regiones Promotoras Genéticas , Telomerasa/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
INTRODUCTION: Rhabdoid Meningiomas (RM) are rare malignant type of meningiomas, classified as grade III in the WHO classification. Only a few case series have been reported, and factors affecting prognosis are still unclear. METHODS: We did a retrospective chart review of all the RMs diagnosed in our institute between 2007 and 2019. Demographic profile, clinical status, imaging, surgical procedures used, post-operative course, adjuvant therapy and follow-ups were reviewed. Histopathological slides were also reviewed. RESULTS: There were 11 patients with RM who underwent 17 surgical procedures between them. Median age was 26 years. On imaging, four had lesions in skull base, three in convexity and four in parasagittal region. Five patients had lesions which had bled and two had leptomeningeal dissemination. Two patients underwent Simpson's grade 1 excision, seven underwent grade 2 and one patient each underwent grade 3 and 5 excisions. One patient presented with poor sensorium and underwent surgery but ultimately succumbed. All reported patients had Rhabdoid features (>50%). Features of anaplasia were seen in four cases and atypical meningioma in others. The median progression-free-survival and overall survival was 6 months and 9 months, respectively. Female gender (n = 5; p = 0.032) and patients who received radiotherapy (p = 0.030) had a survival advantage. Location of the tumor (p = 0.43), presence of hemorrhage in the lesion (p = 0.49), grade of excision (p = 0.40) and WHO pathological grade (p = 0.11) did not have a statistically significant survival benefit. CONCLUSION: Female gender and adjuvant radiotherapy were associated with survival advantage in our sample. Large studies are required to establish the factors associated with survival.
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Neoplasias Meníngeas/patología , Neoplasias Meníngeas/terapia , Meningioma/patología , Meningioma/terapia , Adulto , Terapia Combinada , Femenino , Humanos , Masculino , Neoplasias Meníngeas/mortalidad , Meningioma/mortalidad , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Meningiomas are benign tumors that are treated surgically. Local recurrence is likely if the dura is preserved, and en bloc tumor and dura resection (Simpson grade I) is recommended. In some cases the dura is cauterized and preserved after tumor resection (Simpson grade II). The purpose of this study was performed to analyze clinical features and prognostic factors associated with spinal meningioma, and to identify the most effective surgical treatment. The subjects were 116 patients (22 males, 94 females) with spinal meningioma who underwent surgery at seven NSG centers between 1998 and 2018. Clinical data were collected from the NSG database. Pre- and postoperative neurological status was defined using the modified McCormick scale. The patients had a mean age of 61.2 ± 14.8 years (range 19-91 years) and mean symptom duration of 11.3 ± 14.7 months (range 1-93 months). Complete resection was achieved in 108 cases (94%), including 29 Simpson grade I and 79 Simpson grade II resections. The mean follow-up period was 84.8 ± 52.7 months. At the last follow-up, neurological function had improved in 73 patients (63%), was stable in 34 (29%), and had worsened in 9 (8%). Eight patients had recurrence, and recurrence rates did not differ significantly between Simpson grades I and II in initial surgery. Kaplan-Meier analysis of recurrence-free survival showed that Simpson grade III or IV, male, and dural tail sign were significant factors associated with recurrence (P < 0.05). In conclusion, Simpson I resection is anatomically favorable for spinal meningiomas. Younger male patients with a dural tail and a high-grade tumor require close follow-up. The tumor location and feasibility of surgery can affect the surgical morbidity in Simpson I or II resection. All patients should be carefully monitored for long-term outcomes, and we recommend lifelong surveillance after surgery.
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Duramadre/diagnóstico por imagen , Meningioma/diagnóstico por imagen , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Duramadre/patología , Duramadre/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Meningioma/mortalidad , Meningioma/patología , Meningioma/cirugía , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/mortalidad , Neoplasias de la Columna Vertebral/patología , Neoplasias de la Columna Vertebral/cirugía , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Population aging is likely increasing the number of surgically treated very old (≥ 80-year-old) intracranial meningioma (IM) patients. Since there is little data on mortality in this patient group, we studied whether survival of surgically treated very old IM patients differs from survival of a matched general population. We retrospectively identified 83 consecutive very old IM patients (median age 83 years; 69% women) operated between 2010 and 2018. During the first postoperative year, operated IM patients suffered 2.5 times higher mortality as compared to age- and sex-matched general population but no annual survival difference occurred thereafter. Regarding cumulative estimates, no excess mortality was detected after the second postoperative year. Of the patient who were and who were not able to live at home preoperatively, 78% and 42% lived at home within 3 months, respectively. Preoperative loss of capability to live at home associated with a less frequent return to home [odds ratio (95% confidence interval) 0.21 (0.06-0.67)]. Operated very old IM patients had short-term excess mortality but similar cumulative survival as the matched general population. Moreover, most patients returned home soon after surgery.
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Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/cirugía , Meningioma/mortalidad , Meningioma/cirugía , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Subtotal meningioma resection (STR) is often performed to minimize surgical morbidity. Nevertheless, only a few studies have reported on patient outcome after STR. We studied the long-term outcome of SIV (Simpson grade IV) resection and identified predictive factors of overall survival (OS), progression-free survival (PFS) and time to progression (TTP). METHODS: A retrospective analysis was performed on 68 patients who underwent SIV resection of meningioma (grade I) from 2004 to 2010. Data were collected from clinical, surgical and pathology records and radiological imaging. Long-term outcomes were evaluated at least 10 years after surgery. RESULTS: Permanent morbidity was 11.8%, 30-day mortality 2.9% and progression rate 50.0% for a median follow-up duration of 126.6 months. Median TTP was 86.2 months. Adjuvant SRS was the only significant factor associated with longer PFS (p = 0.0052) and TTP (p = 0.0079). Higher age (p = 0.0022), KPS (p = 0.0182), postoperative ECOG score (p = 0.0182) were reliable predictors of shortened OS and aSRS (p = 0.0445) was reliable predictor of longer OS. CONCLUSION: STR in intracranial meningioma is still viable and often the only treatment option available in high-risk patients or high-risk tumors. Although surgical morbidity and mortality are high, the OS rate was 85.3% at 5 years and 79.4% at 10 years. Because of the considerable progression rate and rather a long term OS the adjuvant SRS should be considered following SIV resection.
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Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/cirugía , Meningioma/mortalidad , Meningioma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Clasificación del Tumor , Supervivencia sin Progresión , Radiocirugia , Radioterapia Adyuvante , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Meningiomas are the most frequent brain tumours occurring after pediatric cranial radiotherapy (CrRT). Data on course of disease, to inform clinical management of meningiomas, are sparse. This study reports the clinical characteristics of histologically confirmed meningiomas in childhood cancer survivors (CCS) in the Netherlands. METHODS: In total, 6015 CCS from the Dutch Long-Term Effects After Childhood Cancer (LATER) cohort were eligible, including 1551 with prior CrRT. These CCS were diagnosed with cancer age <18 y (between 1963 and 2002) and are not subject to brain tumour screening. We identified histologically confirmed meningiomas by record linkage with the Dutch Pathology Registry (PALGA; 1991-2018), and in the Dutch LATER registry. We extracted details regarding diagnosis, treatment, and follow-up from medical records. RESULTS: We described 93 CCS with meningioma, of whom 89 (95.7%) were treated with CrRT (5.7% of 1551 with prior CrRT; OR = 68). Median age at diagnosis was 31.8 y (range: 13.2-50.5). Thirty survivors (32.3%) had synchronous meningiomas; 84 (90.3%) presented with symptoms. Only 16.1% of meningioma was detected at late effects clinics. Over time, all survivors had surgery; one-third also received radiotherapy. During follow-up 38 (40.9%), survivors developed new meningiomas, 22(23.7%) recurrences and at least four died due to the meningioma. CONCLUSIONS: Histologically confirmed meningiomas after childhood cancer are mostly diagnosed with symptoms and not during routine follow-up at late effects clinics. The meningiomas occur at a median of 20-25 y younger age than incidental meningiomas, are frequently multiple and recurrence after treatment is high. It is crucial to inform CCS and healthcare providers about risk and symptoms of subsequent meningiomas.
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Supervivientes de Cáncer , Neoplasias Meníngeas/patología , Meningioma/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Secundarias/patología , Adolescente , Adulto , Edad de Inicio , Femenino , Humanos , Masculino , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/terapia , Meningioma/epidemiología , Meningioma/mortalidad , Meningioma/terapia , Persona de Mediana Edad , Neoplasias Primarias Múltiples/mortalidad , Neoplasias Primarias Múltiples/terapia , Neoplasias Primarias Secundarias/mortalidad , Neoplasias Primarias Secundarias/terapia , Países Bajos/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
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.