Combining FORGE Score and Histopathological Diagnostic Criteria of Atypical Meningioma Enables Risk Stratification of Tumor Progression

Abstract

More than 50% of atypical meningiomas regrow within 5 years after surgery. FORGE score is a newly created tool to estimate the MIB-1 index in cranial meningiomas. In this investigation, we aimed to assess the predictive value of the FORGE score in combination with major diagnostic criteria of atypical meningioma (brain invasion, mitotic count ≥ 4) regarding recurrence in atypical meningiomas. We included patients operated on primary atypical meningiomas in our center from 2011 to 2019. The study included 71 patients (58% women, median age 63 years). ROC curves revealed a superiority of FORGE score combined with histopathological diagnostic criteria of atypical meningioma (AT-FORGE) in the prediction of tumor progression compared to FORGE score only (AUC: 0.72; 95% CI: 0.54–0.91, cut-off: ≥5/<5, sensitivity: 75%, specificity: 78%). Patients with an AT-FORGE score ≥ 5 had a shorter time to tumor progression (32.8 vs. 71.4 months, p < 0.001) in the univariable analysis. Multivariable cox regression analysis revealed significant predictive value of Simpson grade > II, presence of multiple meningiomas and AT-FORGE score ≥ 5 for tumor progression. The combination of histopathological diagnostic criteria for atypical meningioma with FORGE score might facilitate an effective identification of patients with an atypical meningioma who have an increased risk of tumor progression.

Proliferative Potential, and Inflammatory Tumor Microenvironment in Meningioma Correlate with Neurological Function at Presentation and Anatomical Location—From Convexity to Skull Base and Spine

“…Reference curves were used to determine the fibrinogen concentrations. The serum C-reactive protein values were obtained by turbidimetric immunoassays with a CRPL3 reagent (Roche, Basel, Switzerland) [ 16 , 17 , 28 ]. Surgical adverse events were also recorded.…”

“…The proportions of stained and unstained nuclei in the neoplastic cells were determined. Furthermore, semiquantitative investigation and scoring of CD68 − stainings using anti-CD68 antibodies to detect macrophages was performed (Clone KP1, dilution 1:1000, DAKO, Glostrup, Denmark) [ 16 , 17 ]. Semi-quantitative scoring was performed by a senior neuropathologist and tumor specimen were investigated for the absence, focal, or diffuse staining of CD68 macrophages.…”

“…Imaging and clinical follow-up workflow includes the first postoperative MRI scans at 3 months after surgical treatment as well as on an annual basis for the ongoing years. Earlier clinical and imaging examinations were scheduled in case of new or progredient neurological deficits as well as radiological signs of meningioma progression [ 16 , 17 ]. Recurring meningiomas, which regrow at the local cavity of the primary surgery, were considered for analysis.…”

“…Multivariable binary logistic regression analysis was performed to identify variables predicting increased MIB-1 index (≥5%) and density of CD68 + macrophage infiltrates. Dichotomizations of serum CRP (≤1.37 mg/L/>1.37 mg/L) and plasma fibrinogen (≤2.85 g/L/>2.85 g/L) in the prediction of MIB-1 were performed according to previously identified cut-off values for cranial meningiomas [ 16 , 17 ]. Age was dichotomized using the median-split [ 34 ].…”

“…Antibodies can identify the Ki-67 antigen, which is present in the nucleus of cells during the G1, S, and G2 phases of the mitosis as well as cell division cycle [ 13 , 14 , 15 ]. Furthermore, we recently developed a novel scoring sheet using FibrinOgen, C-Reactive protein, Gender, and peritumoral Edema (FORGE score) as a tool to preoperatively estimate the MIB-1 index and the probability of PFS in cranial meningiomas [ 16 , 17 ]. Moreover, it was found that pro-tumor M2 macrophages are more common in both recurrent and WHO grade 2 cranial meningiomas [ 18 ].…”