Johns Hopkins University School of Medicine Baltimore, MD
J. Wang1, R. T. Oglesby2, A. Tran1, M. Miller1, K. Sheikh1, H. Li1, M. Ladra3, W. T. Hrinivich1, and S. Acharya2; 1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD, 3Center for Cancer and Blood Disorders, Childrens National Health System, Washington, DC
Purpose/Objective(s): To characterize the association of linear energy transfer and dose with radiation (RT) necrosis after pencil beam scanning proton therapy in pediatric posterior fossa tumors using a case-control framework. Materials/
Methods: From December 2019 to October 2022, patients = 18 years of age treated with first line proton therapy for primary tumors in the posterior fossa and with at least 6 months of follow up were retrospectively identified. Follow-up MRI scans were assessed for imaging changes concerning for RT necrosis defined as new T1 enhancement +/- T2/FLAIR change within the RT field not associated with tumor recurrence. These necrosis cases were matched with control cases in a 1:2 fashion based on age, sex, dose, and follow-up time from proton therapy. Dose (GyRBE) and dose-averaged LET (LETd) maps were computed in a treatment planning system using Monte Carlo simulation. Voxel-wise data for targets and normal structures were exported and analyzed using a programming environment and R. Comparisons between cases and controls were assessed using Fisher’s exact test and Wilcoxon rank sum test for categorical and continuous variables, respectively. Results: A total of 33 patients met criteria for inclusion in the final analysis (24 controls, 9 cases). Mean age was 6.6 years (STD=4.77) with a median follow up time of 24.1 months. Most common tumors were medulloblastoma (54.5%) and ependymoma (33.3%). Median dose was 54 GyRBE [range 50.4-59.4 GyRBE]. Within the case-control matched cohort (18 controls, 9 cases), there were no significant differences in age, sex, time to follow up, tumor location, dose, and use of concurrent chemotherapy. Mean time to necrotic imaging finding was 4.47 months (STD=2.03). Three patients were symptomatic with ataxia and/or dysmetria, two of whom had multifocal necrosis and one required steroids and bevacizumab. Cases demonstrated significantly higher brainstem D50 (p=0.02) and D40 (p=0.02). Volumetric LETd parameters were not different between cases and controls. However, when using a combined metric of higher brainstem dose (> 47.5GyRBE) and higher LETd (>3.8 keV/µm), a greater proportion of cases compared to controls met this metric (88.9% vs. 42.1%, p=0.04). Conclusion: Combined effects of higher dose and higher LETd may contribute to greater necrosis risk after pencil beam scanning proton therapy in children with posterior fossa tumors.
.jpg "Jarey Wang, MD, PhD photo")