Large-volume PT re-irradiation for recurrent glioma is safe and associated with promising OS outcomes, particularly in the setting of bevacizumab-refractory tumors.
Brijal M. Desai, MD, Russell C. Rockne, PhD, Irene B. Helenowski, MS, PhD, Jeffrey J. Raizer, MD, Nina Paleologos, MD, Ryan Merrell, MD, Sean Grimm, MD, Syed Azeem, MD, William F. Hartsell, MD, Patrick Sweeney, MD, Kristin R. Swanson, PhD, Vinai Gondi, MD; Northwestern University Feinberg School of Medicine; Rush University Medical Center; Northshore University Health Systems; Cadence Brain Tumor Center; CDH Proton Center
BACKGROUND: The therapeutic benefit of targeting T2/fluid-attenuated inversion recovery (FLAIR) in addition to contrast-enhancing (CE) tumor during re-irradiation for recurrent glioma is attenuated by augmented toxicity. Given its steep dose falloff and narrow penumbrae, proton therapy (PT) minimizes the volume of brain parenchyma outside of the target volume, potentially permitting safer delivery of large-volume re-irradiation.
METHODS: From February 2011 to April 2014, a total of 21 consecutive adult patients with recurrent glioma who were treated with PT re-irradiation at a single institution were retrospectively analyzed. Planning target volume (PTV) included T2/FLAIR and CE abnormalities. The covariates that were assessed were age, gender, Karnofsky performance status (KPS) at time of PT, number of pre-PT recurrences, grade at initial diagnosis, interval between PT and prior radiotherapy (PRT), PT dose, PT PTV, bevacizumab failure, concurrent use of temozolomide and/or bevacizumab, and post-PT radiation necrosis. Overall survival (OS) time from PT start was estimated with Kaplan-Meier analysis; comparisons used the log-rank statistic. Multivariate analysis used the Cox proportional hazards model.
RESULTS: Median age was 43 years, and median KPS was 90. The median number of salvage treatments was 2 (range: 1–9). Median interval between PRT and PT was 32.8 months (range: 6.9–162.9 mo). A total of 13 patients (62%) were bevacizumab-refractory. Median PT dose was 50.51 Cobalt Gray Equivalent (CGE), and median PTV was 224.2 cc. Five patients (24%) remain alive. Median OS was 10.5 months overall, 6.3 months among bevacizumab-refractory patients, and 12.4 months among bevacizumab-naive patients. Prior bevacizumab failure (hazard ratio [HR] = 3.77; P = .02), lower KPS score (HR = 1.03; P = .047), and decreased interval between PRT and PT (≤ 40 mo; HR = 3.46; P = .04) were prognostic of inferior OS. On multivariate analysis, decreased interval between PRT and PT (P = .02) remained prognostic of inferior OS, but lower KPS and prior bevacizumab failure trended to significance (P = .07). One patient had grade 3 necrosis in the setting of PT re-irradiation for progressive brainstem glioma. One patient had grade 2 necrosis, and another had grade 2 stroke. No other grade ≥ 3 toxicities were observed.
CONCLUSION: Large-volume PT re-irradiation for recurrent glioma is safe and associated with promising OS outcomes, particularly in the setting of bevacizumab-refractory tumors.
Proceedings of the 97th Annual Meeting of the American Radium Society - americanradiumsociety.org