Atypical and malignant meningiomas: Considerations for treatment and efficacy of radiotherapy

Abstract

The purpose of this study was to add to the current body of literature which is aimed at establishing the role of postoperative adjuvant radiotherapy (RT) in the treatment of atypical and malignant meningiomas. Meningiomas are the most frequently reported primary intracranial tumours, accounting for more than 35%. The majority of meningiomas are benign, with atypical and malignant tumours accounting for only 6–18%. Utilising a prospective multi-institutional database, we retrospectively reviewed 67 patients with documented World Health Organisation (WHO) Grade II/III meningiomas, diagnosed between 1989 and 2012 and resected at two major Australian hospitals. Nine patients were excluded and the remaining 58 were analysed. The patient demographics, tumour characteristics, surgical details and adjuvant therapy were retrieved. Kaplan–Meier curves were used to compare the survival of patients treated with RT versus surgery alone. The 3 year progression free survival (PFS) and overall survival (OS) were 44 and 76% for the entire cohort, respectively. Of the patients who had gross total resections, 42% had 3 years PFS and 77% had 3 years OS, which was not significantly different from those with subtotal resection. The overall median survival was 11.0 years, 12.2 for atypical and 1.6 for malignant meningiomas. The patients with malignant meningiomas were 14 times as likely to receive RT as the patients with atypical meningiomas. The patients who received RT had a 3 year PFS of 63% compared to 40% in those who did not receive radiation. The 3 year OS was 31% higher for females than males. Histopathological progression was noted in 17% of our cohort. This study reinforces a number of important factors that should be considered when treating patients presenting with WHO Grade II and III meningiomas, including sex, potential for grade progression, and the lack of evidence for adjuvant RT and the timing thereof.

Introduction

Meningiomas are the most frequently reported primary intracranial tumours, accounting for more than 35% [1]. The World Health Organization (WHO) classification of central nervous system (CNS) tumours, most recently revised in 2007, classifies meningiomas into Grade I (benign), Grade II (atypical), or Grade III (malignant or anaplastic). Although the majority are benign, atypical and malignant tumours account for 6–18% of all meningiomas, 5–15% and 1–3%, respectively. The recurrence rate for atypical meningiomas is in the range of 30–40%, increasing to 50–80% for malignant meningiomas [2]. A recent study reported the 5 year overall survival (OS) to be 78% for atypical meningiomas, and 44% for malignant meningiomas [3].

Surgery is the mainstay of treatment for patients with an atypical or malignant meningioma. Due to the high recurrence rates for malignant meningiomas, these lesions are also commonly treated with adjuvant external beam radiotherapy (RT), following the initial resection. However, the role of postoperative RT for atypical meningiomas remains controversial. Marcus et al. [4] reported that in these patients, most neurosurgeons (who responded to a questionnaire) would not advocate adjuvant RT if the tumour was completely excised, but the majority would recommend it in patients with subtotal resection (STR).

A recent systematic review documents 10 studies with no significant improvements in outcomes for patients with atypical meningiomas and additional adjuvant RT. In the malignant meningioma arm of the review, only two of the 11 studies reported positive results with RT. The first reported a 24 month progression-free survival (PFS) of 94 versus 61%, but only a trend towards improved 60 month PFS (40 versus 16%). The second study showed adjuvant RT to be a positive prognostic factor for both PFS and OS. There have been three further retrospective studies which showed positive results, but they were not included in this review. Goldsmith et al. reported that the 5 year PFS increased by up to 40% in patients with malignant meningioma who received higher dose RT after subtotal resections [5]. In 2009, Durand et al. reported no statistically significant increase in PFS for patients with malignant meningiomas who underwent postoperative RT, but reported an association with a longer OS (p = 0.036) [3]. A retrospective study of 83 patients with atypical meningioma reported that the addition of adjuvant RT (p = 0.016) and complete tumour resection (p = 0.002) was associated with superior PFS, but did not achieve an increase in OS [6].

It is apparent from the literature that the lack of professional consensus on the role of adjuvant RT stems from the heterogeneity and retrospective nature of the published data; many of the patient cohorts involved data for these relatively uncommon tumours that was collected over decades. The major potential confounding factors include variations in RT time and dose, and the change in the WHO pathological criteria; one study reported that the proportion of WHO Grade III tumours in their cohort reduced from 52 to 21% with the reclassification [7]. The purpose of this study is to add to the current body of literature which is aimed at establishing the role of postoperative adjuvant RT in the treatment of atypical and malignant meningiomas. In addition, we specifically aimed to identify the patient samples that would be suitable for future molecular analysis, particularly of grade progression.