Only 12 patients were able to be followed for 1 year, which resulted in a 33% risk of toxicity among this cohort. The limited follow up in this study makes estimation of the true CNS toxicity somewhat challenging. Larger target size was associated with an increased risk of toxicity; however, we recognize that the small number of events limited the analytic power to identify other possible contributing factors. There may be a tumor size above which treatment with 30 Gy increases the risk of toxicity, necessitating use of a lower dose, but this potential size cutoff remains unknown. We did not observe increased toxicity rates among patients who were prescribed 30 Gy compared with those prescribed 25 Gy in contrast to other reports of higher rates of toxicity with higher doses.18, 28 One possible explanation for the favorable toxicity profile in our study despite dose escalation is the limited follow up and survival of our cohort, which potentially underestimates the toxicity of FSRT as radiation necrosis is often a late effect. An additional explanation for the favorable toxicity profile in the study is that the majority of patients were treated without additional PTV margin, since higher toxicity rates have been suggested with larger margins for patients receiving single-fraction SRS.29 Initial concern for rotational error in treating multiple metastases with a single isocenter resulted in the addition of a PTV margin to some targets; however, the installation of a 6 degree of freedom couch essentially eliminated the potentially observed rotational error making zero margin treatments consistently reproducible.
