Development of the first prediction model for radiation-induced contrast enhancement after proton therapy for posterior fossa tumours in paediatric patients

Background/purpose: Radiation-induced contrast enhancement (RICE) has been identified as a metric of subclinical toxicity. The aim of this study was to develop a normal tissue complication probability (NTCP) model for RICE after proton therapy in paediatric patients with posterior fossa tumours. Materials and methods: Paediatric patients (n = 75) treated with proton radiotherapy (49.6–59.4 Gy (RBE)), focally or in combination with craniospinal axis irradiation, were included. Follow-up magnetic resonance imaging scans were evaluated for RICE. Dose (D), dose multiplied by dose-averaged linear energy transfer (D⋅LETd), organ at risk association, RICE association and age data were extracted to construct a multivariable logistic regression model to predict RICE in voxels. NTCP was calculated using univariable logistic regression with RICE status as the dependent variable and the expected number of RICE voxels as the independent variable. Results: A total of 60 RICE lesions were identified in 23 patients (30.7 %), of which 36 (60 %) were located in the brainstem, primarily the pons. We observed an increased density of RICE voxels in regions with a combination of high D (38.32–55.94 Gy) and medium-to-high LETd (1.89–6.00 keV/µm) values. In addition, younger age and the anatomical location in the pons were identified as independent risk factors for RICE. The NTCP model's optimism corrected area under the receiver operating characteristic curve (AUC) was 0.79, and the Brier score was 0.16. Conclusion: We developed models to predict RICE in paediatric patients. The RICE probability at the voxel- and patient-level increased with D and D⋅LETd, younger age and within the brainstem pons.