and purpose: To characterize patterns and outcomes of brain MR image changes after proton therapy (PT) for skull base head and neck cancer (HNC). Material and methods: 127 patients treated with PT for HNC who had received at least 40 Gy(RBE) to the brain and had at least 1 follow up MRI > 6 months after PT were analyzed. MRIs were reviewed for radiation-associated image changes (RAIC). MRIs were rigidly registered to planning CTs, and RAIC were contoured on T1 (post contrast) and T2 weighted

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... uences, and dose volume parameters extracted. Probability of RAIC over time was calculated using multistate analysis. Univariate/multivariate analyses were performed using Cox Regression. Recursive partitioning analysis was used to investigate dose volume correlates of RAIC development. Results: 17.3% developed RAIC. All RAIC events were asymptomatic and occurred in the temporal lobe (14), frontal lobe (6) and cerebellum (2). The median volume of the RAIC on post contrast T1 was 0.5 cc at their maximum size. The RAIC spontaneously resolved in 27.3%, progressed in 27.3% and improved or were stable in 29.6% of patients. The three year actuarial rate of developing RAIC was 14.3%. Brain and RAIC lesion doses were generally higher for temporal lobe RAIC compared to frontal lobe RAIC. RAIC was observed in 63% of patients when V67 Gy(RBE) of the brain exceeded 0.17 cc. Conclusion: RAIC lesions after PT were asymptomatic and either resolved or regressed in the majority of the patients. The estimated dose volume correlations confirm the importance of minimizing focal high doses to brain when achievable.