Based on the review of our cohort of 72 cases and the published literature, RON is a rare complication after external beam radiation therapy in patients with NFA. We found no case of RON in our cohort. Our literature review found a total of 11 adequately documented cases of RON in series reports of radiation-treated NFA patients for an overall incidence of 0.53%. This is significantly lower than the 1.36% incidence of RON in acromegalic patients23 (P = 0.01; odds ratio 2.56; 95% CI, 1.26-5.22). One possible determinant contributing to the relatively increased incidence of RON in GH-secreting pituitary ade-nomas compared to NFAs is the occurrence of more microvascular damage in association with GH excess12.
An additional 14 RON cases emerged from single case reports. Reviewing the total of 25 cases, we found that RON usually occurred between 12 and 18 months after radiation treatment but could occur after a considerably longer latency period. Previous reports do indicate that a total radiation dose greater than 50 Gy and/or a daily radiation fraction size greater than 2 Gy are risk factors for developing RON19,24, although RON can occur at lower doses14,19.
In as many as 33% of reported cases, we could identify no risk factors related to radiation therapy. Older age has been touted as a possible risk factor for RON9,25, but our series suggests that age is not a strong risk factor for developing RON in NFA, given the median age of 52 years at the start of radiation therapy among our patients. Our review also found no major gender predominance for the development of RON.
Based on these results, the current dose-fractionation policy in our department is 45 Gy in 1.8 Gy fractions for all pituitary adenomas. According to McCollough et al.26, there is no benefit in applying a higher total dose.