PURPOSE: Craniopharyngiomas are benign, slow-growing tumors that frequently contain a cystic component. Even with gross total resection, the cyst can reform and cause symptoms. Fluctuations in cyst volume during radiotherapy (RT) can affect treatment planning and delivery. The aim of this study was to report our experience with cyst enlargement during conformal proton RT for children with craniopharyngioma and to make recommendations regarding mid-treatment surveillance. METHODS AND MATERIALS: Between January 2001 and August 2007, 24 children (aged <or=18 years) underwent proton RT at the Massachusetts General Hospital for craniopharyngioma. For all 24 patients, tumor size on magnetic resonance imaging and/or computed tomography was measured before and after RT. Surveillance imaging was available for review on 17 patients. During RT, cyst growth was assessed to determine whether the treatment fields needed to be altered. RESULTS: Of the 17 children who underwent repeat imaging during RT, 6 required intervention because of changes in cyst dimensions. Four patients (24%) had cyst growth beyond the original treatment fields, requiring enlargement of the treatment plan. One patient's treatment field was reduced after a decreased in cyst size. Cyst drainage was performed in another patient to avoid enlargement of the treatment fields. CONCLUSION: In patients undergoing highly conformal RT for craniopharyngiomas with cysts, routine imaging during treatment is recommended. Surveillance imaging should be performed at least every 2 weeks during proton RT in an attempt to avoid marginal failure. Craniopharyngiomas with large cystic components or enlargement during treatment might require weekly imaging.