Recurrence Of Atypical Meningiomas Research Articles

Recurrence Rate and Risk Factors of Atypical Meningioma:a Meta-analysis

Objective To systematically review the overall status of postoperative recurrence in patients with atypical meningiomas. Methods China National Knowledge Infrastructure,Wanfang Database,Chinese Biomedical Literature Database,VIP Database,PubMed,Embase,Web of Science,and Cochrane Library were searched for collection of the relevant literature on the recurrence of atypical meningioma from database establishment to July 2021.Two investigators independently screened the literature,extracted data,and assessed the risk of bias of the included studies,and then performed a meta-analysis by using R 5.0. Results A total of 29 studies involving 3122 patients were included in this study.The meta-analysis showed that the overall postoperative recurrence rate of atypical meningioma was 38%.The subgroup analysis showed that the tumor recurrence rate of patients ≥60 years old and<60 years old was 51% and 40%,respectively,with no significant difference.The tumor recurrence rates in male and female patients were 42% and 44%,respectively,which showed no significant difference.The recurrence rates of the patients with parasagittal meningiomas,brain tissue infiltration,Ki-67>8%,mitotic count ≥6/10 high-power fields,and tissue necrosis were 52%,47%,63%,53%,and 69%,respectively.The recurrence rate after subtotal tumor resection was as high as 58%,and the patients who received radiotherapy had higher tumor recurrence rate than that those who did not receive radiotherapy (38% vs.29%,P=0.007). Conclusions The current evidence demonstrates that atypical meningioma has a high recurrence rate after surgery.It is essential to pay more attention and take corresponding measures to improve the tumor-free survival rate of the patients.

Ki67 Index Is the Most Powerful Factor for Predicting the Recurrence in Atypical Meningioma : Retrospective Analysis of 99 Patients in Two Institutes.

ObjectiveThe primary objective of this study was to identify predicting factors for local control (LC) of atypical meningioma, and we validated them with comparing the predicting factors for recurrence-free survival (RFS). We also examined the rate of LC after surgical resection with or without adjuvant treatment and RFS. MethodsClinical and radiological records of patients with atypical meningiomas diagnosed at two institutes from January 2000 to December 2018 were reviewed retrospectively. Histopathological features were also reviewed using formalin-fixed paraffin embedded samples from pathological archives. ResultsOf the 99 atypical meningiomas eligible for analysis, 36 (36.4%) recurred during the follow-up period (mean, 83.3 months; range, 12–232 months). The rate of 3-year LC and 5-year LC was 80.8% and 74.7%, respectively. The mean time-to-recurrence was 49.4 months (range, 12–150). The mean RFS was 149.3 months (95% confidence interval, 128.8–169.8 months) during the mean follow-up duration of 83.3 months (range, 12–232 months). Multivariate analysis using Cox proportional-hazard regression model showed that the extent of resection (hazard ratio [HR], 4.761; p=0.013), Ki67 index (HR, 8.541; p=0.004), mitotic index (HR, 3.275; p=0.044), and tumor size (HR, 3.228; p=0.041) were independently associated with LC. These factors were also statistically associated with RFS. In terms of radiotherapy after surgical resection, the recurrence was not prevented by immediate radiotherapy because of the strong effect of proliferative index on recurrence. ConclusionThe present study suggests that the extent of resection, proliferative index (according to Ki67 expression) and mitotic index, and tumor size are associated with recurrence of atypical meningiomas. However, our results should be further validated through prospective and randomized clinical trials to overcome the inborn bias of retrospective nature of the study design.

Establishment and Validation of an Integrated Model to Predict Postoperative Recurrence in Patients With Atypical Meningioma.

BackgroundThis study aims to establish an integrated model based on clinical, laboratory, radiological, and pathological factors to predict the postoperative recurrence of atypical meningioma (AM).Materials and MethodsA retrospective study of 183 patients with AM was conducted. Patients were randomly divided into a training cohort (n = 128) and an external validation cohort (n = 55). Univariable and multivariable Cox regression analyses, the least absolute shrinkage and selection operator (LASSO) regression analysis, time-dependent receiver operating characteristic (ROC) curve analysis, and evaluation of clinical usage were used to select variables for the final nomogram model.ResultsAfter multivariable Cox analysis, serum fibrinogen >2.95 g/L (hazard ratio (HR), 2.43; 95% confidence interval (CI), 1.05–5.63; p = 0.039), tumor located in skull base (HR, 6.59; 95% CI, 2.46-17.68; p < 0.001), Simpson grades III–IV (HR, 2.73; 95% CI, 1.01–7.34; p = 0.047), tumor diameter >4.91 cm (HR, 7.10; 95% CI, 2.52–19.95; p < 0.001), and mitotic level ≥4/high power field (HR, 2.80; 95% CI, 1.16–6.74; p = 0.021) were independently associated with AM recurrence. Mitotic level was excluded after LASSO analysis, and it did not improve the predictive performance and clinical usage of the model. Therefore, the other four factors were integrated into the nomogram model, which showed good discrimination abilities in training cohort (C-index, 0.822; 95% CI, 0.759–0.885) and validation cohort (C-index, 0.817; 95% CI, 0.716–0.918) and good match between the predicted and observed probability of recurrence-free survival.ConclusionOur study established an integrated model to predict the postoperative recurrence of AM.

Postoperative radiation therapy (PORT) impact on clinical outcomes of resected atypical meningioma: A meta-analysis.

2570 Background: Although meningiomas are among the most prevalent types of brain tumors, atypical meningiomas (AM) account for around 4% of all meningiomas. AMs tend to be more aggressive with relatively higher rates of recurrence and mortality. Gross total resection (GTR) has been the standard of care when possible. However, GTR itself is not always enough to prevent recurrence of AMs. The role of PORT remains controversial in AM as the comparative studies to support its use have provided conflicting results. The purpose of this meta-analysis is to evaluate the impact of PORT on clinical outcomes in resected AMs. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of (i) AM diagnosis, (ii) English language, (iii) Simpson graded resections, and (iv) comparative studies reporting recurrence rates (RcR), Progression Free Survival (PFS), and Overall Survival (OS) with hazard ratios (HR) or Kaplan-Meier curves. A meta-analysis was conducted using an inverse variance method with random-effects model. Results: Twenty-two comparative studies with a total of 5,129 patients were included and analyzed. When GTR was attained, PORT was associated with improved RcR (HR = 0.72, 95%CI:0.59-0.86) and PFS (HR = 0.77, 95%CI:0.65-0.90), but not OS (HR = 0.93, 95%CI:0.83-1.04). When subtotal resection (STR) was attained, PORT was associated with improved PFS (HR = 0.35, 95%CI:0.26-0.48) as well as OS (HR = 0.70, 95%CI:0.54-0.89). Conclusions: This is the first meta-analysis to show that PORT is associated with PFS benefit in AMs with GTR and STR. Moreover, PORT significantly improved OS of AMs that underwent STR but had no impact on OS when GTR was achieved. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the use of PORT in this patient population.

Factors Related to the Post-operative Recurrence of Atypical Meningiomas.

Aim: This study aimed to investigate the relationship between clinicopathological characteristics of atypical meningiomas (AM) and its post-operative recurrence.Materials and Methods: The clinicopathological characteristics and findings from follow up were retrospectively reviewed and compared between AM and benign meningioma (BM) patients. Univariate and multivariate analyses were employed to identify the factors related to the post-operative recurrence of AM.Results: More BM patients were females and received complete resection; the recurrence rate was significantly lower in BM patients as compared to AM patients. The progesterone receptor (PR), E-cadherin protein (E-Ca) and β-catenin positive rates and Ki67 labeling index were significantly different between two groups. Univariate analysis showed the age, tumor size, tumor invasiveness, E-Ca expression, and extent of resection were related to the post-operative recurrence of AM. However, multivariate analysis showed only the extent of resection and tumor invasiveness were the independent factors associated with the post-operative recurrence of AM.Conclusions: The extent of resection and tumor invasiveness are related to the post-operative recurrence of AM. To improve the surgical procedures to maximize the tumor resection is important to improve the prognosis of AM patients.

Dysregulation of Apoptosis Caused by Aberrant Histone Modification Influences on the Recurrence of Meningiomas

Background: Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study was aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. Materials and method: The medical records of 67 patients with AMs, as diagnosed during recent 13 years, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5). Results: Twenty-six (38.8%) patients recurred during the follow-up period (mean duration 47.7 months). In terms of time-to-recurrence (TTR), overexpression of CASP3, TRAIL-R1, and BAX had a longer TTR than underexpression, and overexpression of Survivin, MDM2, and BCL2 had a shorter TTR than underexpression (P<0.05). Additionally, overexpression of MLL2, UTX, and JMJ5 had shorter TTRs than underexpression, and overexpression of KDM5c had a longer TTR than underexpression. However, in the multi-variate analysis of predicting factors for recurrence, underexpression of CASP3 (P<0.001), and BAX (P<0.001), and overexpression of survivin (P=0.007), and MDM2 (P=0.037) were associated with recurrence independently, but any enzymes modifying histone were not associated with recurrence. Conclusion: This study suggests certain apoptosis-associated factors should be associated with recurrence of AMs, which may be regulated epigenetically by histone modifying enzymes.

Treatment Response and Prognosis After Recurrence of Atypical Meningiomas

Intracranial atypical meningiomas have a greater rate of recurrence than benign meningiomas. Scant literature, however, is available regarding the treatment and prognosis of these tumors after recurrence. The objective of this study was to analyze the treatment outcomes and prognostic factors of atypical meningiomas after recurrence of disease. Forty-one cases with clinical characteristics and follow-up data were available in our department from 2000 to 2013. Certain factors, such as sex, age, preoperative Karnofsky Performance Status Scale score, location, prerecurrence tumor precursor, interval time, Simpson grade, histologic grade after recurrence, and radiotherapy, were selected to study the relationship with the prognosis of the tumors. The mean progression-free survival (PFS) and overall survival (OS) in our cases were 40.5 ± 4.7 and 57.1 ± 5.8 months, respectively. The 1-, 3-, and 5-year PFS rates were 79.8%, 44.1%, and 39.2%, respectively, and the corresponding OS rates were 92.4%, 66.1%, and 48.8%, respectively. The precursors of recurrent tumors were transformed meningiomas, an interval time less than 24 months, and a postrecurrence histologic diagnosis of anaplastic meningioma might predict an unfavorable outcome. Surgery Simpson I and II can improve the PFS and OS of tumors. Because of the limited number of cases, we could not identify a relationship between radiotherapy and prognosis. Recurrent atypical meningiomas are intractable tumors with a high rate of recurrence and death. Total resection of the tumors under relatively safe conditions remains the most suitable treatment strategy.

Epigenetic Role of Histone 3 Lysine Methyltransferase and Demethylase in Regulating Apoptosis Predicting the Recurrence of Atypical Meningioma.

Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. The medical records of 67 patients with AMs, as diagnosed during recent 13 yr, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5). Twenty-six (38.8%) patients recurred during the follow-up period (mean duration 47.7 months). In terms of time-to-recurrence (TTR), overexpression of CASP3, TRAIL-R1, and BAX had a longer TTR than low expression, and overexpression of survivin, MDM2, and BCL2 had a shorter TTR than low expression (P<0.05). Additionally, overexpression of MLL2, UTX, and JMJ5 had shorter TTRs than low expression, and overexpression of KDM5c had a longer TTR than low expression. However, in the multi-variate analysis of predicting factors for recurrence, low expression of CASP3 (P<0.001), and BAX (P<0.001), and overexpression of survivin (P=0.007), and MDM2 (P=0.037) were associated with recurrence independently, but any enzymes modifying histone were not associated with recurrence. Conclusively, this study suggests certain apoptosis-associated factors should be associated with recurrence of AMs, which may be regulated epigenetically by histone modifying enzymes.

Long-term survival analysis of atypical meningiomas: survival rates, prognostic factors, operative and radiotherapy treatment.

The rarity and the inconsistent criteria for defining atypical meningioma prior to the WHO 2007 classification made its management and prognostic factors poorly understood. Only few articles have addressed the survival rates of WHO-classified atypical meningiomas. The small number or the disproportionate representation of irradiated patients was a weakness for these articles. This study evaluated whether the extent of surgery and receiving adjuvant radiotherapy after an initial operation along with other patient characteristics influenced the recurrence and survival rates of atypical meningiomas. The clinical and surgical notes of the 79 patients with grade II atypical meningioma treated at our center over 13 years were retrospectively evaluated. The histology grading was consistent with WHO 2007 classification. The Simpson grading system was used to assess the extent of surgical resection. Kaplan Meier analysis, Cox multivariate regression analysis, and the Log-rank test were conducted using STATA® statistical package. The average age at the time of initial operation was 58 years, and 54 % were males. The mean follow-up period was 50 months. In Cox multivariate analysis, only Simpson grading was predictive of recurrence (hazard ratio = 2.22 / 1 increase in Simpson grade. p = 0.003). Simpson grade I patients had a relapse-free survival rate of 97 and 74 % at one and five years, respectively, compared with 88 and 32 % in the subtotal resection group (Simpson grades II to IV). There was no statistically significant correlation between recurrence and subjecting patients to postoperative radiotherapy. Apart from Simpson grade I patients, there was a general trend for worse outcome in irradiated patients. The most important prognostic factor in determining recurrence was Simpson grading. There was no statistically significant impact of adjuvant radiotherapy on the recurrence of atypical meningiomas. Meta-analysis for the existing literature is needed.

Early gross recurrence of atypical meningioma

Early gross recurrence of atypical meningioma