The Role of Adjuvant Radiotherapy in Atypical (Who Grade II) Meningiomas: Meta-Analysis and Systematic Review of Literature

Introduction: Well recognized as the most common nonglial CNS tumors, Meningiomas is now believed to be the commonest primary CNS neoplasm in adults constituting 35.6% of all primary CNS tumors with an incidence of 7.44 per 100,000 population according to the latest U.S. population study. Recent revisions to the Histopathological classification of meningiomas have resulted in an exponential increase in the diagnosis of Grade II tumors. The role of upfront adjuvant radiotherapy in WHO grade II remains controversial especially following gross total resection. The aim of this study is to analyze the role of adjuvant radiotherapy in WHO grade II meningiomas

Methods: The literature was extensively reviewed using SCOPUS, PubMed, MEDLINE (EBSCO), Wiley InterScience Journals (includes Cochrane), ScienceDirect (Elsevier), and Oxford University Press. We used the search terms “atypical meningioma” or “WHO grade II Meningioma” and “radiotherapy,” “radiation therapy” or “stereotactic radiotherapy.” We included all studies on patients with grade II meningioma who followed the release of the WHO 2000 classification. Our exclusion criteria were as follows: (1) Primary radiation therapy, (2) studies with no specified number of grade II tumors, (3) those with no confirmed histopathological grading or grading that predates the WHO 2000 classification, and (4) outcome reported on mixed grades II and III cohorts. We extracted demographic (age and gender) and tumor characteristics (location and grade), therapies (extent of resection and radiotherapy), and outcome data (recurrence and survival).

Results: A total of 23 studies were included in our final analysis (n = 1575) of which 45.93% were males. Tumor location was distributed as convexity 40.1%, parasagittal/falcine 27.4% and other, including skull base 32.4%. Overall PFS at 5 and 10 years was 55.5% (n = 753) and 39.1% (n = 556), respectively. Meta-analysis of 12 studies directly comparing ART to surgery alone, revealed a combined relative risk in favor of ART (RR, 0.734; 95% CI, 0.31–1.19; p = 0.041). Subgroup analysis showed a trend for earlier progression following subtotal resection (STR) as compared with gross total resection (GTR) regardless of ART. Recurrence rates were comparable after STR with and without ART (42.5 vs. 42.9%, p = 0.966). Nevertheless, there was a significant reduction in recurrence rates with ART following GTR (27.4 vs. 16.3%, p = 0.0363).

Conclusion: On the basis of this literature review, it seems that WHO grade II meningiomas are associated with 55.5 and 39.1% progression free survival at 5 and 10 years, respectively, despite treatment. Subgroup analysis indicated gross total resection followed by radiotherapy stands the best chances of preventing or delaying recurrence in these tumors. It is therefore our recommendation to aim for GTR followed by radiotherapy until a multicenter randomized controlled trial in the future confirms otherwise.