Timing of Adjuvant Radiotherapy in Atypical Meningiomas

Abstract

The optimal timing of adjuvant radiotherapy (RT) in the management of atypical meningiomas remains controversial. We sought to compare the outcomes of surgically resected atypical meningiomas managed with upfront adjuvant RT vs. initial surveillance. Patients with World Health Organization (WHO) Grade II (atypical) meningiomas who underwent surgical resection between 2000-2015 and were followed at our institution were identified. Clinical, histopathological, and treatment-related variables were compared between patients who received adjuvant RT, defined as RT received within the first year of surgery before tumor progression/recurrence (P/R), vs. those who initially underwent surveillance. The primary endpoints were radiographic evidence of progression/recurrence (P/R) and time to P/R. The secondary endpoint was overall survival (OS). Cox proportional hazards modeling was used to analyze time to tumor P/R and OS. Kaplan-Meier analysis was used to calculate the actuarial rates of P/R and death. The log-rank test was used to compare the Kaplan-Meier curves. A total of 230 patients with atypical meningiomas were identified. Median follow-up was 6.9 years. Median age was 57. Sixty percent were female and 94% had a Karnofsky performance status (KPS) ≥70. Five percent had a remote history of cranial irradiation. Median tumor size was 4.7 cm. Tumor locations were convexity (46%), skull base (32%), parafalcine (21%), and intraventricular (1%). Surgical outcome was gross total resection (GTR) in 151 (66%) and subtotal resection (STR) in 79 (34%) patients. Postoperatively, 51 (22%) patients received upfront adjuvant RT while 179 (78%) initially underwent surveillance alone. Compared to the surveillance group, patients who received adjuvant RT had larger tumors (5.2 cm vs. 4.6 cm; p = 0.04), were more likely to have undergone STR vs. GTR (65% vs. 26%; p<0.01), and more often had bone invasion (18% vs. 7%; p = 0.02). On multivariable analysis adjusted for sex, prior cranial irradiation, tumor size, extent of resection (EOR), mitotic activity, and brain invasion, receipt of adjuvant RT was independently associated with a lower risk of P/R compared to surveillance (HR = 0.21 [95% CI 0.11-0.41]; p<0.01). Patients who initially underwent surveillance and then received salvage RT at time of P/R had a shorter median time to local progression after RT compared to patients who developed local P/R following upfront adjuvant RT (19 vs. 64 months, respectively; p<0.01). There was no difference in overall survival (OS) with adjuvant RT vs. initial surveillance (5-year OS 91% [95% CI 0.78-0.97] vs. 94% [95% CI 0.89-0.97], respectively; log-rank p = 0.95). Upfront adjuvant RT was associated with improved local control in atypical meningiomas irrespective of EOR as compared to initial surveillance. Early adjuvant RT should be considered in certain patients with atypical meningiomas regardless of EOR.