WHO Grade I Meningioma Recurrence: Identifying High Risk Patients Using Histopathological Features and the MIB-1 Index

Abstract

Objective: In this study, we identify clinical, radiographic, and histopathologic prognosticators of overall, early, and post-median recurrence in World Health Organization (WHO) grade I meningiomas. We also determine a clinically relevant cutoff for MIB-1 to identify patients at high risk for recurrence. Method: A retrospective review of WHO grade I meningioma patients with available MIB-1 index data who underwent treatment at our institution from 2007 to 2017 was performed. Univariate and multivariate analyses, and recursive partitioning analysis (RPA), were used to identify risk factors for overall, early (within 24 months), and post-median (>24 months post-treatment) recurrence. Result: A total of 239 patients were included. The mean age was 60.0 years, and 69.5% of patients were female. The average follow-up was 41.1 months. All patients received surgery and 2 patients each received either adjuvant radiotherapy (2/239) or gamma knife treatment (2/239). The incidence of recurrence was 10.9% (26/239 patients), with an average time to recurrence of 33.2 months (6-105 months). Posterior fossa tumor location (p = 0.004), MIB-1 staining (p = 0.008), nuclear atypia (p = 0.003), and STR (p < 0.001) were independently associated with an increased risk of recurrence on cox-regression analysis. RPA for overall recurrence highlighted extent of resection, and after gross total resection (GTR), a MIB-1 index cutoff of 4.5% as key prognostic factors for recurrence. Patients with a GTR and MIB-1 >4.5% had a similar incidence of recurrence as those with STR (18.8 vs. 18.6%). Variables independently associated with early recurrence on binary logistic regression modeling included STR (p = 0.002) and nuclear atypia (p = 0.019). RPA confirmed STR as associated with early recurrence. Conclusion: STR, posterior fossa location, nuclear atypia, and elevated MIB-1 index are prognostic factors for WHO grade I meningioma recurrence. Moreover, MIB-1 index >4.5% is prognostic for recurrence in patients with GTR. Verification of our findings in larger, multi-institutional studies could enable risk stratification and recommendations for adjuvant radiotherapy following resection of WHO grade I meningiomas.

Keywords: MIB-1; WHO grade I; benign; early recurrence; late recurrence; meningioma; recurrence.

Figure 1

Kaplan Meier curves of risk factors for WHO grade I meningioma recurrence. (A) Nuclear atypia (blue line) vs. no nuclear atypia (red line) (X² = 2.21, p = 0.137). (B) Posterior-fossa tumor location (blue line) vs. other locations (red line) (X² = 10.36, p = 0.001). (C) MIB-1 index >4.5% (blue line) vs. ≤4.5% (red line) (X² = 6.17, p = 0.013). (D) STR (blue line) vs. GTR (red line) (X² = 10.46, p = 0.001).

Figure 2

Recursive partitioning analysis highlighting key risk factors for (A) overall recurrence, (B) post-median recurrence, and (C) early recurrence.