Post-Radiation Treatment Changes in Meningioma Patients: A Comparative Analysis of Proton and Photon Therapy

Summary: External beam radiation therapy is a mainstay of treatment for meningioma. Recently, proton therapy has emerged as a prominent alternative to photon (x-ray) radiation. While proton therapy improves normal tissue sparing, the end-of-range radiobiological effects could lead to a higher risk of radiation necrosis of the treatment area. This study compares the incidence of radiation-induced brain injury in meningioma patients treated with proton therapy versus photon therapy. A total of 61 WHO Grade I, II, or III meningioma patients treated at a tertiary center were retrospectively analyzed. Of these, 30 received proton therapy and 31 received photon therapy. All patients had received radiation to either the meningioma itself or the surgical cavity post-resection, with doses ranging from 50 Gy to 60 Gy over 25 to 33 fractions. We identified post-radiation worsening T1-weighted contrast enhancement (T1CE) or T2/FLAIR changes on imaging that is not attributable to tumor progression. Post-radiation changes were classified as symptomatic if patients exhibited radiation-related symptoms and/or required treatments such as corticosteroids, bevacizumab, hyperbaric oxygen, or surgery. Symptom severity was classified using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. We found a significantly higher incidence of post-radiation imaging changes in patients treated with proton therapy compared to photon therapy. Specifically, 14 of 30 proton therapy patients exhibited post-radiation changes, compared to 6 of 31 photon therapy patients (p=0.031). Median follow-up time was 19.7 months for proton therapy and 47.2 months for photon therapy. The median time from the end of radiation treatment to initial imaging enhancement was 4.5 months for proton therapy and 7.6 months for photon therapy, while the median time to first radiation-related symptoms was 12.2 months for proton therapy and 7.6 months for photon therapy. While symptomatic post-radiation changes were elevated in proton therapy patients, with 7 of 30 proton patients classified as symptomatic compared to 2 of 31 photon therapy patients, this difference was not statistically significant (p=0.081). In the proton therapy cohort, 2 patients had grade 1 adverse events (AE), 4 had grade 2 AE, and 1 had grade 3 AE. In the photon therapy cohort, 1 patient had a grade 1 AE and 1 had a grade 3 AE. This study indicates that proton therapy may be associated with a higher risk of asymptomatic and symptomatic post-radiation imaging changes for meningioma patients. An imbalance in follow-up time between groups may affect long-term results; further analysis and large-scale studies are necessary to confirm these findings and/or rule out other contributing factors. Despite these limitations, the results suggest that proton therapy, while beneficial in sparing normal tissue, may increase the risk of post-radiation changes in the treatment area due to its higher biologically effective dose. Aren S. Saini, BS (Presenting Author) - University of Miami Miller School of Medicine; Kayla Samimi, BS (Co-Author) - University of Miami Miller School of Medicine; Raksha M. Narasimhan, BS (Co-Author) - University of Miami Miller School of Medicine; Chiara La Tessa, PhD (Co-Author) - Sylvester Comprehensive Cancer Center; Michael Butkus, PhD (Co-Author) - Sylvester Comprehensive Cancer Center; Eric A. Mellon, MD, PhD (Co-Author) - Sylvester Comprehensive Cancer Center