Brain injury after proton therapy or carbon ion therapy for head-and-neck cancer and skull base tumors

Purpose To assess the incidence of early delayed or late morbidity of the brain after particle therapy for skull base tumors and head-and-neck cancers. Methods and Materials Between May 2001 and December 2005, 59 patients with cancerous invasion of the skull base were treated with proton or carbon ion therapy at the Hyogo Ion Beam Medical Center. Adverse events were assessed according to the magnetic resonance imaging findings (late effects of normal tissue-subjective, objective, management, analytic [LENT-SOMA]) and symptoms (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0). Dose–volume histograms were used to analyze the relationship between the dose and volume of the irradiated brain and the occurrence of brain injury. The median follow-up time was 33 months. Results Of the 48 patients treated with proton therapy and 11 patients treated with carbon ion radiotherapy, 8 (17%) and 7 (64%), respectively, developed radiation-induced brain changes (RIBCs) on magnetic resonance imaging (LENT-SOMA Grade 1-3). Four patients (7%) had some clinical symptoms, such as vertigo and headache (CTCAE Grade 2) or epilepsy (CTCAE Grade 3). The actuarial occurrence rate of RIBCs at 2 and 3 years was 20% and 39%, respectively, with a significant difference in the incidence between the proton and carbon ion radiotherapy groups. The dose–volume histogram analyses revealed significant differences between the brain lobes with and without RIBCs in the actuarial volume of brain lobes receiving high doses. Conclusion Particle therapies produced minimal symptomatic brain toxicities, but sequential evaluation with magnetic resonance imaging detected a greater incidence of RIBCs. Significant differences were observed in the irradiated brain volume between the brain lobes with and without RIBCs.