A Clinical Prognostic Model Based on Preoperative Hematological and Clinical Parameters Predicts the Progression of Primary WHO Grade II Meningioma.

PURPOSE: The purpose was to explore the correlation between hematological parameters and the progression of WHO grade II meningioma, and establish a clinical prognostic model based on hematological parameters and clinical prognostic factors to predict the progression-free survival (PFS) of patients. METHODS: A total of 274 patients with WHO grade II meningiomas were included. Patients were randomly divided into a training cohort (192, 70%) and a test cohort (82, 30%). In the training cohort, the least absolute shrinkage and selection operator Cox regression analysis were used to screen for hematological parameters with prognostic value, and the hematological risk model (HRM) was constructed based on these parameters; univariate and multivariate Cox regression analyses were utilized to screen for clinical prognostic factors, and a clinical prognostic model was constructed based on clinical prognostic factors and HRM. The prognostic stability and accuracy of the HRM and clinical prognostic model were verified in the test cohort. Subgroup analysis was performed according to the patients' different clinical characteristics. RESULTS: Preoperative neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, albumin-to-globulin ratio, D-dimer, fibrinogen, and lactate dehydrogenase were associated with the PFS of patients. The areas under curve of the HRM were 0.773 (95% confidence interval [CI] 0.707-0.839) and 0.745 (95% CI 0.637-0.852) in the training cohort and test cohort, respectively. The progression risk was higher in the high-risk group than that in the low-risk group categorized by the optimal cutoff value (2.05) of hematological risk scores. The HRM, age, tumor location, tumor size, peritumoral edema, extent of resection, Ki-67 index, and postoperative radiotherapy were the prognostic factors for the progression of meningiomas. The corrected C-index of the clinical prognosis model was 0.79 in the training cohort. Clinical decision analysis showed that the clinical prognostic model could be used to obtain favorable clinical benefits. In the subgroup analysis, the HRM displayed excellent prognostic stability and general applicability in different subgroups. CONCLUSIONS: Preoperative hematological parameters are associated with the postoperative progression of WHO grade II meningiomas. The clinical prognosis model constructed based on hematological parameters and clinical prognostic factors has favorable predictive accuracy and clinical benefits.

Clear cell histology portends a worse prognosis than other WHO grade II histologies.

PURPOSE: Clear cell meningioma (CCM) is a rare WHO grade II meningioma variant, characterized by aggressive features and a high tumor recurrence rate. In this study, we compared overall and progression-free survivals between CCMs and other WHO grade II meningiomas. METHODS: A retrospective institutional database review was performed to identify all patients who underwent surgical resection of a WHO grade II meningioma between 1997 and 2019. Overall survival and progression-free survival were compared between patients with clear cell meningiomas and patients with other WHO grade II meningiomas. Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and survival. RESULTS: We included a total of 214 patients in this study (43 CCMs, 171 other WHO grade II meningiomas). Patients with CCMs had significantly shorter progression-free (p = 0.001) and overall (p = 0.026) survivals than patients with other grade II meningiomas. In multivariable analysis, clear cell histology was a significant and powerful independent predictor of tumor recurrence (HR 1.93; 95% CI 1.14-3.26) when controlling for tumor location, extent of resection, and adjuvant radiation. In multivariable analysis, clear cell histology correlated with increased mortality (HR 1.96, 95% CI 0.97-3.94), though this was not statistically significant. CONCLUSION: This is the first study to compare overall and progression-free survivals between CCMs and other WHO grade II meningiomas. Clear cell histology predicts a higher risk of tumor recurrence and mortality than other grade II histologies. Future studies may help to understand the impact of these findings and the treatment implications.

Extent of resection and survival outcomes in World Health Organization grade II meningiomas.

PURPOSE: WHO grade II meningiomas behave aggressively, with recurrence rates as high as 60%. Although complete resection in low-grade meningiomas is associated with a relatively low recurrence rate, the impact of complete resection for WHO grade II meningiomas is less clear. We studied the association of extent of resection with overall and progression-free survivals in patients with WHO grade II meningiomas. METHODS: A retrospective database review was performed to identify all patients who underwent surgical resection for intracranial WHO grade II meningiomas at our institution between 1995 and 2019. Kaplan-Meier analysis was used to compare overall and progression-free survivals between patients who underwent gross total resection (GTR) and those who underwent subtotal resection (STR). Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and mortality. RESULTS: Of 214 patients who underwent surgical resection for WHO grade II meningiomas (median follow-up 53.4 months), 158 had GTR and 56 had STR. In Kaplan-Meier analysis, patients who underwent GTR had significantly longer progression-free (p = 0.002) and overall (p = 0.006) survivals than those who underwent STR. In multivariable Cox proportional-hazards analysis, GTR independently predicted prolonged progression-free (HR 0.57, p = 0.038) and overall (HR 0.44, p = 0.017) survivals when controlling for age, tumor location, and adjuvant radiation. CONCLUSIONS: Extent of resection independently predicts progression-free and overall survivals in patients with WHO grade II meningiomas. In an era of increasing support for adjuvant treatment modalities in the management of meningiomas, our data support maximal safe resection as the primary goal in treatment of these patients.

Review of Atypical and Anaplastic Meningiomas: Classification, Molecular Biology, and Management.

Although the majority of meningiomas are slow-growing and benign, atypical and anaplastic meningiomas behave aggressively with a penchant for recurrence. Standard of care includes surgical resection followed by adjuvant radiation in anaplastic and partially resected atypical meningiomas; however, the role of adjuvant radiation for incompletely resected atypical meningiomas remains debated. Despite maximum treatment, atypical, and anaplastic meningiomas have a strong proclivity for recurrence. Accumulating mutations over time, recurrent tumors behave more aggressively and often become refractory or no longer amenable to further surgical resection or radiation. Chemotherapy and other medical therapies are available as salvage treatment once standard options are exhausted; however, efficacy of these agents remains limited. This review discusses the risk factors, classification, and molecular biology of meningiomas as well as the current management strategies, novel therapeutic approaches, and future directions for managing atypical and anaplastic meningiomas.

Clear Cell Meningioma: A Clinicopathologic Study of a Rare Meningioma Subtype in 35 Patients.

OBJECTIVE: Clear cell meningioma (CCM) is a rare histologic variant, accounting for only 0.2%-0.8% of all meningiomas. Given their relative infrequency, few cases have been reported. We have presented one of the largest series of patients with intracranial CCM and reported the treatments and outcomes of these patients. METHODS: Patients with histologically proven CCM from 2003 to 2018 were identified for inclusion in the present study. Relevant clinical and radiographic data were obtained via retrospective review and analyzed. Kaplan-Meier and Cox proportional hazards analyses were used to compare overall and progression-free survival. RESULTS: A total of 35 patients had undergone surgical resection for CCM, including 18 women and 17 men, with a mean age of 59.3 years. Gross total resection was achieved in 22 patients (62.9%), and 11 patients (31.4%) had received adjuvant postoperative radiotherapy. Tumors recurred in 17 patients (48.6%), with a mean time to recurrence of 31.3 months. The mean postoperative follow-up was 66.3 months. On multivariable analysis, adjuvant radiotherapy and gross total tumor resection were both independently associated with prolonged progression-free survival (P < 0.033), although not with overall survival (P >0.274). CONCLUSIONS: The data from the present series of 35 patients with CCM have shown distinct contrasts to previous series, with an older mean age and a nearly 1:1 male/female ratio. Although gross total resection and adjuvant postoperative radiotherapy were both independently associated with longer progression-free survival for patients with CCM, tumor recurrence has remained a challenge in the treatment of these patients.

Atypical meningioma. A study on recurrence and disease-specific survival.

BACKGROUND: To analyse the outcome of patients with WHO grade II meningioma and identify factors that may influence recurrence and survival. MATERIAL AND METHODS: Between January 2000 and October 2016, a retrospective search identified 215 WHO grade II meningiomas operated on at our institution. A survival analysis was conducted on clinical and histological criteria. RESULTS: Eighteen patients (8.4%) had a previous history of grade I meningioma. The cohort underwent a total of 302 surgical resections and 29.7% received radiotherapy. Forty-one patients (19.1%) had been re-operated on for a WHO grade II meningioma relapse. Median follow-up was 4.5 years. At the end of the study, 105 patients (53.6%) had no residual tumour on the last scan. Surgical recurrence-free survival at 5 years was 82%, 95% CI [75.9-88.5]. Secondary grade II meningioma (HR=4.27, P=0.001), Simpson resection grade 1 and 2 vs. 3, 4 and 5 (HR=0.25, P=0.001) and, Ki-67 index (HR=0.22, P<0.001) were independently associated with the surgical recurrence-free survival. Forty-four patients died from their tumours (20.5%). Cause-specific survival probability at 5 years was 83.2%, 95% CI [77.6-89.1]. Age at diagnosis (HR=0.31, P<0.001), Simpson resection grade 1 and 2 vs. 3, 4 and 5 (HR=0.32, P<0.001) and, redo surgery for recurrence (HR=2.39, P=0.010) were independently associated with the cause-specific survival. Patients who received radiotherapy did not demonstrate either a reduced risk of recurrence or a longer survival (P=0.280). CONCLUSION: In this large series, atypical meningioma recurrence correlated with progression from grade I to II, incomplete resection and high Ki-67 index; shorter survival with an older age, incomplete resection, and redo surgery for recurrence. We did not observe a significant improvement in any of the clinical outcomes after radiotherapy.

Overall survival benefit associated with adjuvant radiotherapy in WHO grade II meningioma.

BACKGROUND: Adjuvant radiotherapy (RT) after surgical resection of World Health Organization (WHO) grade II meningioma, also known as atypical meningioma (AM), is a topic of controversy. The purpose of this study is to compare overall survival (OS) with or without adjuvant RT after subtotal resection (STR) or gross total resection (GTR) in AM patients diagnosed according to the 2007 WHO classification. METHODS: The National Cancer Database was used to identify 2515 patients who were diagnosed with AM between 2009 and 2012 and underwent STR or GTR with or without adjuvant RT. Propensity score matching was first applied to balance covariates including age, year of diagnosis, sex, race, histology, and tumor size in STR or GTR cohorts stratified by adjuvant RT status. Multivariate regression according to the Cox proportional hazards model and Kaplan-Meier survival plots with log-rank test were then used to evaluate OS difference associated with adjuvant RT. RESULTS: GTR is associated with improved OS compared with STR. In the subgroup analysis, adjuvant RT in patients who underwent STR demonstrated significant association with improved OS compared with no adjuvant RT (adjusted hazard ratio [AHR] 0.590, P = .045); however, adjuvant RT is not associated with improved OS in patients who underwent GTR (AHR 1.093, P = .737). CONCLUSIONS: Despite the lack of consensus on whether adjuvant RT reduces recurrence after surgical resection of AM, our study observed significantly improved OS with adjuvant RT compared with no adjuvant RT after STR.

Recent advances in the management of atypical meningiomas.

Based on the 2007 WHO classification, the proportion of atypical meningiomas has steeply increased. Complete resection is usually considered curative, however, the recurrence rate remains high. The treatment of more aggressive meningiomas remains problematic. We performed a literature review via the PubMed database with specific attention to radiological, pathological, genetic and molecular aspects particular to WHO grade II meningiomas and current therapeutic strategies. We also reviewed the role of surgery and summarized the results of the principal studies dealing with adjuvant strategies based on the most recent evidence. Adjuvant radiotherapy, administered as stereotactic radiosurgery or conventional external beam irradiation, should be strongly considered in selected cases. Limited data exist regarding the role of hormonal treatment or chemotherapy as adjunct therapy. A target therapy modulating the altered molecular balance may be the key to revolutionize the prognosis of these patients.

WHO grade II meningioma: a retrospective study for outcome and prognostic factor assessment.

To analyse the outcome of patients with WHO grade II meningioma and identify factors that may influence recurrence and survival. Between January 2007 and September 2015, a retrospective search identified 194 WHO grade II meningiomas at the National Hospital for Neurology and Neurosurgery, London. Survival methods were implemented. 31 patients (16 %) had a previous history of grade I meningioma. The patients underwent a total of 344 surgical resections and 43.3 % received radiotherapy. 55 patients (28.4 %) had been re-operated on for a WHO grade II meningioma relapse. Median follow-up was 4.4 years. At the end of the study, 75 patients (40.1 %) had no residual tumour on the last scan. Surgical recurrence free survival at 5 years was 71.6, 95 % CI [63.5, 80.8]. Secondary grade II meningioma (HR = 2.29, p = 0.010), and, Simpson resection grade 1, 2 and 3 vs. 4 and 5 (HR = 0.57, p = 0.050) were associated with the surgical recurrence-free survival. 32 died from meningioma (16.5 %). Overall survival probability at 5 years was 83.2, 95 % CI [76.6, 90.4]. Age at diagnosis (HR = 0.22, p < 0.001), WHO grade I meningioma progressing into grade II (HR = 3.2, p = 0.001), tumour location (HR = 0.19, p < 0.001), and mitosis count (HR = 0.36, p = 0.010) were independently associated with the overall survival. Patients who received radiotherapy demonstrated neither a reduced risk of recurrence nor a longer overall survival (p = 0.310). In our series shorter survival correlated with older age, increased mitoses, progression from grade I to II and location. We were not able to demonstrate a significant improvement in any of the clinical outcomes after radiotherapy.

World Health Organization grade II meningiomas.

BACKGROUND: We analyzed WHO grade II meningioma cases to identify factors influencing survival. MATERIALS AND METHODS: Between January 2000 and August 2015, 206 cases of World Health Organization (WHO) grade II meningioma were operated at our institution. This population underwent a total of 298 surgical resections and 55 patients received a radiotherapy. A Cox multivariate regression was conducted on clinical and histological criteria. RESULTS: Sixty-four patients were deceased (31.1 %), of which 38 died following the disease progression (18.4 %). Overall survival probability at 1, 5, and 10 years were 95.4 %, 95 % CI [92.5, 98.4]; 84 %, 95 % CI [78.3, 90.2], and 72.9 %, 95 % CI [64.5, 82.4], respectively (Fig. 1a). At the end of the study, only 87 patients (42.2 %) were alive with no tumor residual or recurrence on the last scan. Age at diagnosis (hazard ratio (HR) = 0.31, 95 % CI [0.15, 0.63], p < 0.001), extent of resection (HR = 0.25, 95 % CI [0.12, 0.49], p < 0.001), and tumoral brain invasion (HR = 0.49, 95 % CI [0.25, 0.98], p = 0.040) were independent factors associated with the overall survival. The patients who received radiotherapy did not demonstrate a longer overall survival (p = 0.540). CONCLUSIONS: WHO grade II meningioma significantly impaired the survival of the patients. In the adjusted Cox regression, a macroscopic gross total resection (Simpson grades 1, 2, and 3), an age below 62 years at diagnosis and the absence of brain invasion were independent factors associated with a longer survival. Radiotherapy may not increase the overall survival after complete or incomplete resection.

World Health Organization Grade II Meningioma: A 10-Year Retrospective Study for Recurrence and Prognostic Factor Assessment.

BACKGROUND: We analyzed the characteristics of patients with World Health Organization (WHO) Grade II meningioma to identify factors that may influence recurrence. MATERIALS AND METHODS: Between January 2000 and August 2015, 178 cases of WHO Grade II meningioma were operated at our institution. This population underwent a total of 224 surgical resections, and 36 patients received radiotherapy. Median follow-up was 3.6 years, and interquartile range was 1.5-6.2. RESULTS: A total of 28 patients (16.1%) were re operated for a relapse of their Grade II meningioma. The median time between the first and the second surgery was 4.2 years [interquartile range 1.4-5.3]. Surgical recurrence-free survival at 1, 2, 5, and 10 years were: 96.9% (95% confidence interval [95% CI] 94.2-99.6; 91.7%, 95% CI 87.3-96.3; 85%, 95% CI 78.6-92; and 70.8%, 95% CI 60.1-83.5), respectively. At the end of the study, 93 patients (57.8%) had no residual tumor on the last scan. Age at diagnosis (hazard ratio [HR] 0.17, 95% CI 0.05-0.56, P < 0.001), extent of resection (HR 0.22, 95% CI 0.08-0.64, P = 0.01), and Ki-67 index (HR 0.18, 95% CI 0.06-0.56, P < 0.001) were independent factors associated with the surgical recurrence-free survival. CONCLUSIONS: Younger patients with a lower proliferation rate and gross total resection are less likely to undergo a reintervention for WHO Grade II meningioma recurrence. Observation rather than systematic adjuvant radiotherapy may be preferred. If possible, a redo surgery may be considered in case of relapse or tumor residual progression, because radiotherapy may not decrease the surgical recurrence-free survival after complete or incomplete resection.