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1.
Acta Neurochir (Wien) ; 166(1): 282, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967664

ABSTRACT

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.


Subject(s)
Databases, Factual , Meningeal Neoplasms , Meningioma , Humans , Meningioma/epidemiology , Meningioma/mortality , Meningioma/pathology , Aged , Male , Middle Aged , Female , Aged, 80 and over , Meningeal Neoplasms/epidemiology , Meningeal Neoplasms/mortality , Meningeal Neoplasms/pathology , United States/epidemiology , Age Factors , Neoplasm Grading
2.
Appl Immunohistochem Mol Morphol ; 32(6): 292-304, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38863278

ABSTRACT

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.


Subject(s)
Forkhead Box Protein M1 , Immunohistochemistry , Matrix Metalloproteinase 9 , Meningioma , Humans , Forkhead Box Protein M1/metabolism , Meningioma/metabolism , Meningioma/pathology , Meningioma/mortality , Female , Male , Matrix Metalloproteinase 9/metabolism , Middle Aged , Adult , Aged , Neoplasm Grading , Biomarkers, Tumor/metabolism , Ki-67 Antigen/metabolism , Meningeal Neoplasms/pathology , Meningeal Neoplasms/metabolism , Meningeal Neoplasms/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/metabolism , Gene Expression Regulation, Neoplastic
3.
PLoS One ; 19(5): e0303337, 2024.
Article in English | MEDLINE | ID: mdl-38758750

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor , Meningeal Neoplasms , Meningioma , Meningioma/metabolism , Meningioma/pathology , Meningioma/mortality , Meningioma/diagnosis , Humans , Biomarkers, Tumor/metabolism , Prognosis , Meningeal Neoplasms/metabolism , Meningeal Neoplasms/mortality , Meningeal Neoplasms/pathology , Meningeal Neoplasms/diagnosis , DNA Topoisomerases, Type II/metabolism , Ki-67 Antigen/metabolism , Tumor Suppressor Protein p53/metabolism , Vascular Endothelial Growth Factor A/metabolism , Immunohistochemistry , Poly-ADP-Ribose Binding Proteins
4.
World Neurosurg ; 187: e331-e339, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38649022

ABSTRACT

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.


Subject(s)
Meningeal Neoplasms , Meningioma , Neoplasm Grading , Neoplasm Recurrence, Local , World Health Organization , Humans , Meningioma/surgery , Meningioma/pathology , Meningioma/mortality , Female , Male , Middle Aged , Meningeal Neoplasms/surgery , Meningeal Neoplasms/pathology , Meningeal Neoplasms/mortality , Prognosis , Adult , Aged , Treatment Outcome , Retrospective Studies , Young Adult , Adolescent , Neurosurgical Procedures/methods , Kaplan-Meier Estimate , Aged, 80 and over
5.
World Neurosurg ; 186: e342-e352, 2024 06.
Article in English | MEDLINE | ID: mdl-38570092

ABSTRACT

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.


Subject(s)
Meningeal Neoplasms , Meningioma , Neoplasm Recurrence, Local , Humans , Meningioma/mortality , Meningioma/surgery , Meningioma/diagnostic imaging , Meningioma/pathology , Male , Female , Middle Aged , Aged , Meningeal Neoplasms/mortality , Meningeal Neoplasms/surgery , Meningeal Neoplasms/pathology , Meningeal Neoplasms/diagnostic imaging , Adult , Aged, 80 and over , Retrospective Studies , Cohort Studies , Magnetic Resonance Imaging , Follow-Up Studies
6.
Radiother Oncol ; 195: 110271, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38588920

ABSTRACT

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.


Subject(s)
Meningeal Neoplasms , Meningioma , Neoplasm Recurrence, Local , Re-Irradiation , Humans , Meningioma/radiotherapy , Meningioma/pathology , Meningioma/mortality , Male , Female , Aged , Middle Aged , Re-Irradiation/methods , Re-Irradiation/adverse effects , Neoplasm Recurrence, Local/radiotherapy , Adult , Aged, 80 and over , Prognosis , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/pathology , Meningeal Neoplasms/mortality , Young Adult , Treatment Outcome , Retrospective Studies
8.
Cancer Sci ; 113(2): 697-708, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34839570

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Furans/therapeutic use , Ketones/therapeutic use , Meningeal Neoplasms/drug therapy , Meningioma/drug therapy , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Furans/pharmacology , Humans , Kaplan-Meier Estimate , Ketones/pharmacology , Meningeal Neoplasms/genetics , Meningeal Neoplasms/mortality , Meningeal Neoplasms/pathology , Meningioma/genetics , Meningioma/mortality , Meningioma/pathology , Mice , Mutation , Promoter Regions, Genetic , Telomerase/genetics , Xenograft Model Antitumor Assays
9.
Clin Neurol Neurosurg ; 207: 106778, 2021 08.
Article in English | MEDLINE | ID: mdl-34214868

ABSTRACT

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.


Subject(s)
Meningeal Neoplasms/pathology , Meningeal Neoplasms/therapy , Meningioma/pathology , Meningioma/therapy , Adult , Combined Modality Therapy , Female , Humans , Male , Meningeal Neoplasms/mortality , Meningioma/mortality , Middle Aged , Neoplasm Grading , Prognosis , Retrospective Studies , Survival Rate , Young Adult
10.
Clin Neurol Neurosurg ; 207: 106766, 2021 08.
Article in English | MEDLINE | ID: mdl-34166979

ABSTRACT

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.


Subject(s)
Meningeal Neoplasms/mortality , Meningeal Neoplasms/surgery , Meningioma/mortality , Meningioma/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Meningeal Neoplasms/pathology , Meningioma/pathology , Middle Aged , Neoplasm Grading , Progression-Free Survival , Radiosurgery , Radiotherapy, Adjuvant , Retrospective Studies , Survival Rate , Time Factors , Treatment Outcome
11.
Sci Rep ; 11(1): 11630, 2021 06 02.
Article in English | MEDLINE | ID: mdl-34079036

ABSTRACT

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.


Subject(s)
Dura Mater/diagnostic imaging , Meningioma/diagnostic imaging , Spinal Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , Dura Mater/pathology , Dura Mater/surgery , Female , Humans , Magnetic Resonance Imaging , Male , Meningioma/mortality , Meningioma/pathology , Meningioma/surgery , Middle Aged , Neoplasm Grading , Prognosis , Retrospective Studies , Spinal Neoplasms/mortality , Spinal Neoplasms/pathology , Spinal Neoplasms/surgery , Survival Analysis , Treatment Outcome
12.
Sci Rep ; 11(1): 11454, 2021 06 01.
Article in English | MEDLINE | ID: mdl-34075085

ABSTRACT

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.


Subject(s)
Meningeal Neoplasms/mortality , Meningeal Neoplasms/surgery , Meningioma/mortality , Meningioma/surgery , Aged, 80 and over , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Survival Rate
13.
Brain ; 144(11): 3322-3327, 2021 12 16.
Article in English | MEDLINE | ID: mdl-33974079

ABSTRACT

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.


Subject(s)
Brain Neoplasms/complications , Brain Neoplasms/mortality , Epilepsy/etiology , Cohort Studies , Female , Glioblastoma/complications , Glioblastoma/mortality , Humans , Male , Meningeal Neoplasms/complications , Meningeal Neoplasms/mortality , Meningioma/complications , Meningioma/mortality , Prognosis , Progression-Free Survival
14.
Eur J Cancer ; 150: 240-249, 2021 06.
Article in English | MEDLINE | ID: mdl-33934061

ABSTRACT

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.


Subject(s)
Cancer Survivors , Meningeal Neoplasms/pathology , Meningioma/pathology , Neoplasms, Multiple Primary/pathology , Neoplasms, Second Primary/pathology , Adolescent , Adult , Age of Onset , Female , Humans , Male , Meningeal Neoplasms/mortality , Meningeal Neoplasms/therapy , Meningioma/epidemiology , Meningioma/mortality , Meningioma/therapy , Middle Aged , Neoplasms, Multiple Primary/mortality , Neoplasms, Multiple Primary/therapy , Neoplasms, Second Primary/mortality , Neoplasms, Second Primary/therapy , Netherlands/epidemiology , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young Adult
15.
Brain Tumor Pathol ; 38(3): 156-172, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33903981

ABSTRACT

Meningiomas are the most commonly diagnosed benign intracranial adult tumors. Subsets of meningiomas that present with extensive invasion into surrounding brain areas have high recurrence rates, resulting in difficulties for complete resection, substantially increased mortality of patients, and are therapeutically challenging for neurosurgeons. Exciting new data have provided insights into the understanding of the molecular machinery of invasion. Moreover, clinical trials for several novel approaches have been launched. Here, we will highlight the mechanisms which govern brain invasion and new promising therapeutic approaches for brain-invasive meningiomas, including pharmacological approaches targeting three major aspects of tumor cell invasion: extracellular matrix degradation, cell adhesion, and growth factors, as well as other innovative treatments such as immunotherapy, hormone therapy, Tumor Treating Fields, and biodegradable copolymers (wafers), impregnated chemotherapy. Those ongoing studies can offer more diversified possibilities of potential treatments for brain-invasive meningiomas, and help to increase the survival benefits for patients.


Subject(s)
Brain Neoplasms/pathology , Brain Neoplasms/therapy , Meningeal Neoplasms/pathology , Meningeal Neoplasms/therapy , Meningioma/pathology , Meningioma/therapy , Antineoplastic Agents/administration & dosage , Brain Neoplasms/genetics , Brain Neoplasms/mortality , Cell Adhesion , Disease-Free Survival , Extracellular Matrix/pathology , Humans , Immunotherapy , Intercellular Signaling Peptides and Proteins , Meningeal Neoplasms/genetics , Meningeal Neoplasms/mortality , Meningioma/genetics , Meningioma/mortality , Molecular Targeted Therapy , Neoplasm Invasiveness/genetics
16.
BMC Cancer ; 21(1): 211, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33648471

ABSTRACT

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


Subject(s)
Biomarkers, Tumor/analysis , Meningeal Neoplasms/metabolism , Meningioma/metabolism , Aged , Algorithms , Choline/metabolism , Cluster Analysis , Disease Progression , Female , Glycine/metabolism , Humans , Male , Meningeal Neoplasms/chemistry , Meningeal Neoplasms/mortality , Meningioma/chemistry , Meningioma/mortality , Middle Aged , Neoplasm Grading , Nuclear Magnetic Resonance, Biomolecular , Progression-Free Survival , Serine/metabolism , Treatment Outcome , Tryptophan/metabolism
17.
Acta Neurochir (Wien) ; 163(6): 1665-1675, 2021 06.
Article in English | MEDLINE | ID: mdl-33751215

ABSTRACT

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


Subject(s)
Incidental Findings , Meningeal Neoplasms/pathology , Meningioma/pathology , Adult , Aged , Aged, 80 and over , Cell Proliferation , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/surgery , Meningioma/mortality , Meningioma/radiotherapy , Meningioma/surgery , Middle Aged , Morbidity , Progression-Free Survival , Proportional Hazards Models , Prospective Studies , Risk Factors , Treatment Outcome
18.
Cancer Treat Res Commun ; 27: 100343, 2021.
Article in English | MEDLINE | ID: mdl-33647870

ABSTRACT

BACKGROUND: No large-scale study evaluating the usefulness of tamoxifen after meningioma surgery has been undertaken. METHODS: We processed the French Système National des Données de Santé (SNDS) database using an algorithm combining the type of surgical procedure and the International Classification of Diseases to retrieve cases of meningiomas operated between 2007 and 2017. Survival analyses were performed using a matched cohort study. RESULTS: 251 patients treated by tamoxifen were extracted from a nationwide population-based cohort of 28 924 patients operated on for a meningioma over a 10-year period. 94% were female and median age at meningioma first surgery was 57 years IQR[47-67]. Tamoxifen treatment median duration was 1.4 years IQR[0.4-3.2]. Tamoxifen treatment median cumulative given dose was 11.4 gs, IQR[3.6-24.9]. There was a strong positive correlation between treatment duration and cumulative dose (τ=0.81, p<0.001). 6% of the patient had to be reoperated for a meningioma recurrence and 26.3% had radiotherapy. OS rates at 5 and 10 years were: 92.3%, 95%CI[90.3-94.3] and 81.3%, 95%CI[75.2-88] respectively. These 251 patients were matched by gender, age at surgery and grade with the same number of subjects within the nationwide cohort. Nor overall (HR=1.46, 95%CI[0.86- 2.49], p=0.163) or progression-free survival (HR=1.2, 95%CI[0.89- 1.62], p=0.239) were significantly improved by the tamoxifen treatment. CONCLUSION: Using this unique database, in the setting of breast cancer, we could not conclude on a favourable effect of tamoxifen to prevent recurrence after meningioma surgery or to increase meningioma-related survival even in case of prolonged treatment duration or high cumulative given dose.


Subject(s)
Chemotherapy, Adjuvant/statistics & numerical data , Meningeal Neoplasms/therapy , Meningioma/therapy , Neoplasm Recurrence, Local/epidemiology , Tamoxifen/administration & dosage , Aged , Chemoradiotherapy, Adjuvant/methods , Chemoradiotherapy, Adjuvant/statistics & numerical data , Chemotherapy, Adjuvant/methods , Databases, Factual , Dose-Response Relationship, Drug , Female , France/epidemiology , Humans , Male , Meningeal Neoplasms/mortality , Meninges/pathology , Meninges/surgery , Meningioma/mortality , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/therapy , Progression-Free Survival , Retrospective Studies , Survival Analysis , Time Factors
19.
World Neurosurg ; 150: e324-e336, 2021 06.
Article in English | MEDLINE | ID: mdl-33727203

ABSTRACT

BACKGROUND: The use of stereotactic radiosurgery for the treatment of intracranial meningiomas has been established as an effective and safe treatment modality. Larger meningiomas typically are managed by surgery followed by radiosurgery. Treatment of large meningiomas (usually defined as >10 cc) by stereotactic radiosurgery has been investigated in some recent reports, either by single-session, volume-staged, or the hypofractionation technique. We sought to assess the long-term efficacy and safety of single-session stereotactic radiosurgery for large (10 cc or more) intracranial benign meningiomas. PATIENTS AND METHODS: In this retrospective study, we included 273 patients with large benign meningiomas (≥10 cc) who were treated by single-session SRS and followed up for more than 2 years. Tumors were in a basal location in 228 patients (84%). There were 161 tumors (59%) in the perioptic location. The median tumor volume was 15.5 (10-57.3 cc [interquartile range {IQR} 12.3 cc]). The median prescription dose was 12 Gy (9-15 Gy [IQR 1 Gy]). RESULTS: The median follow-up period was 6.1 years (2-18 years [IQR 5.5 years]). The tumor control rate was 90%. The progression-free survival at 5 and 10 years was 96% and 81%, respectively, for the whole cohort. Among 161 patients with perioptic meningiomas, favorable (better/stable) visual outcome was reported in 155 patients (96%) and unfavorable (worse) outcome in 6 patients (4%). Temporary adverse radiation effects were observed in 41 patients (15%) but only 16 (6%) were symptomatic. CONCLUSIONS: Stereotactic radiosurgery provides an effective and safe treatment option for large meningiomas.


Subject(s)
Brain Neoplasms/surgery , Meningioma/surgery , Neurosurgical Procedures/methods , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Brain Neoplasms/mortality , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Meningioma/mortality , Middle Aged , Neurosurgical Procedures/adverse effects , Neurosurgical Procedures/mortality , Progression-Free Survival , Radiation Dosage , Radiosurgery/adverse effects , Radiosurgery/mortality , Retrospective Studies , Skull Base Neoplasms/surgery , Treatment Outcome , Vision, Ocular , Young Adult
20.
Eur J Surg Oncol ; 47(9): 2340-2345, 2021 09.
Article in English | MEDLINE | ID: mdl-33546961

ABSTRACT

BACKGROUND: The objective of this study is to determine the population-based estimates of the epidemiology, incidence, and outcomes of spinal meningiomas. METHODS: The data of patients with spinal meningiomas diagnosed between 2004 and 2016 were extracted from the SEER database. Descriptive analyses were conducted to evaluate the distribution and tumor-related characteristics of patients with spinal meningiomas. Multivariate logistic regression analysis was performed to predict which patients were inclined to be diagnosed with borderline or malignant spinal meningiomas. Possible prognostic indicators were analyzed by Kaplan-Meier curves and the Cox proportional hazards model. RESULTS: The age-adjusted incidence rate was 0.37 cases per 1,000,000 person-years between 2004 and 2016. Spinal meningiomas represented 4.25% of all meningiomas. A total of 4204 patients with spinal meningiomas were included in our study. Most of the patients were white and diagnosed at 60-69 years of age, and the female:male ratio was 4:1. Most of the tumors were benign and less than 3 cm in size. The most common pathological type was psammomatous meningioma. Surgery was the first choice of treatment for patients with spinal meningiomas. Male and pediatric patients were more vulnerable to borderline or malignant spinal meningiomas. Survival analysis showed that married, female, and younger patients with benign meningiomas had better overall survival than their counterparts. CONCLUSION: Spinal meningiomas are relatively rare lesions with a favorable prognosis. Psammomatous meningioma is the most common subtype. Male and pediatric patients are more frequently diagnosed with borderline or malignant spinal meningiomas. Surgery is the primary choice of treatment.


Subject(s)
Meningeal Neoplasms/epidemiology , Meningioma/epidemiology , Spinal Cord Neoplasms/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Incidence , Kaplan-Meier Estimate , Male , Marital Status , Meningeal Neoplasms/mortality , Meningeal Neoplasms/pathology , Meningioma/mortality , Meningioma/pathology , Middle Aged , SEER Program , Sex Factors , Spinal Cord Neoplasms/mortality , Spinal Cord Neoplasms/pathology , Survival Rate , United States/epidemiology , Young Adult
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