FORGE: A Novel Scoring System to Predict the MIB-1 Labeling Index in Intracranial Meningiomas

Abstract

The MIB-1 index is an essential predictor of progression-free-survival (PFS) in meningioma. To date, the MIB-1 index is not available in preoperative treatment planning. A preoperative score estimating the MIB-1 index in patients with intracranial meningiomas has not been investigated so far. Between 2013 and 2019, 208 patients with tumor morphology data, MIB-1 index data, and plasma fibrinogen and serum C-reactive protein (CRP) data underwent surgery for intracranial WHO grade I and II meningioma. An optimal MIB-1 index cut-off value (≥6/<6) in the prediction of recurrence was determined by ROC curve analysis (AUC: 0.71; 95% CI: 0.55–0.87). A high MIB-1 index (≥6%) was present in 50 cases (24.0%) and was significantly associated with male sex, peritumoral edema, low baseline CRP, and low fibrinogen level in the multivariate analysis. A scoring system (“FORGE”) based on sex, peritumoral edema, preoperative CRP value, and plasma fibrinogen level supports prediction of the MIB-1 index (sensitivity 62%, specificity 79%). The MIB-1 labeling index and the FORGE score are significantly associated with an increased risk of poor PFS time. We suggest a novel score (“FORGE”) to preoperatively estimate the risk of an increased MIB-1 index (≥6%), which might help in surgical decision making and follow-up interval determination and inform future trials investigating inflammatory burden and proliferative activity.

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

“…Clinical data including age, sex, comorbidities, Karnofsky performance status (KPS), body mass index (BMI), smoking, acetylsalicylic acid (ASA) intake, tumor size, peritumoral brain edema, tumor growth characteristics, WHO classification based on postoperative neuropathological examination, immunohistochemical examinations, extent of meningioma resection based on the Simpson grading system according to the European Association of Neuro-Oncology (EANO) (Simpson grade 1-3 = gross total resection, Simpson grade 4 = subtotal resection, and Simpson grade 5 = biopsy), and postoperative follow-up data were recorded and saved in a computerized database as previously reported (SPSS, v27 for Mac, IBM Corp., Armonk, NY, USA) [16,19]. Preoperative diagnostic workflow included MR imaging of the brain within 48 h before surgical resection.…”

“…Preoperative diagnostic workflow included MR imaging of the brain within 48 h before surgical resection. Tumor size was measured using a diameter-based technique in which the single largest diameter on a single axial preoperative contrast-enhanced T1-weighted MR slice was selected [16,20]. Peritumoral edema was defined as a hyperintense signal adjacent to tumors on T2-weighed MR-images [16,21].…”

“…Tumor size was measured using a diameter-based technique in which the single largest diameter on a single axial preoperative contrast-enhanced T1-weighted MR slice was selected [16,20]. Peritumoral edema was defined as a hyperintense signal adjacent to tumors on T2-weighed MR-images [16,21]. Laboratory parameters were collected using the laboratory information system Lauris (v.17.06.21, Swisslab GmbH, Berlin, Germany).…”

“…Reference curves were used to determine the concentration of fibrinogen. The serum CRP levels were obtained by turbidimetric immunoassays with a CRPL3 reagent (Roche, Basel, Switzerland) [16,22].…”

“…Therefore, the prognostic impact of MIB-1 remains to be further investigated [15]. For preoperative estimation of the MIB-1 labeling index, and hence preoperative estimation of the progression-free survival in newly diagnosed cranial meningiomas, we recently developed a novel scoring system using FibrinOgen, C-Reactive protein, Gender, and peritumoral Edema (FORGE score) [16]. Therefore, the scoring sheet includes preoperative systemic inflammatory parameters reflecting the inflammatory burden (i.e., fibrinogen and C-reactive protein (CRP)), gender, and the presence of peritumoral edema which are all easily determinable variables and facilitate personalized medical decision making.…”