Pattern of Failure Analysis and Clinical Outcomes in Patients With Grade 2 Meningiomas Following Radiation Therapy.

Abstract

Grade 2 meningiomas often recur after surgery and radiation therapy. However, large, in-depth failure analyses are lacking, limiting the potential to refine radiation therapy. We report a pattern of failure analysis, encompassing treatment and outcome data from over 2 decades. Patients who underwent proton- or photon-based fractionated adjuvant or salvage radiation therapy for a grade 2 meningioma between 2000 and 2023 were included. Subsequently, an in-depth analysis of the failure pattern was conducted. A total of 105 patients were included, with 36 patients having 46 progressive or recurrent grade 2 meningiomas during the available follow-up. Most patients received 59.4 Gy (interquartile range [IQR] 57.6-59.4) in 33 fractions (62.9%) and underwent proton radiation therapy (61.0%), with a median voxel-based equivalent uniform dose (EUD) of 60.1 Gy (IQR, 57.3-61.3). Most recurrent and progressive tumors were either located in the treatment volume (35/46, 76.1%) or within 2 cm of it (9/46, 19.6%). The median distance to out-of-field failures was 11.9 mm. The EUD (hazard ratio [HR], 0.77, 95% confidence interval [CI], 0.59-0.98), target volume (HR, 1.6; 95% CI, 1.2-2.1), RTOG 0539 risk classification (high vs intermediate, HR, 7.9; 95% CI, 1.5-42.7), male sex (HR, 2.0; 95% CI, 0.9-4.4), treatment indication (salvage vs adjuvant, HR, 2.4; 95% CI, 1.1-5.5), and age at radiation therapy (HR, 1.5; 95% CI, 1.0-2.1) were associated with progression. This in-depth pattern of failure analysis for grade 2 meningiomas after radiation therapy demonstrated that treatment failures predominantly occur in close spatial relation to the irradiated target volume. Large treatment volumes, macroscopic disease, and a low EUD considerably impact disease control, underscoring the need for further local treatment and targeting refinements.