Biological Effective Dose as a Predictor of Hypopituitarism After Single-Fraction Pituitary Adenoma Radiosurgery: Dosimetric Analysis and Cohort Study of Patients Treated Using Contemporary Techniques

BACKGROUND: Hypopituitarism is the most frequent complication after pituitary adenoma stereotactic radiosurgery (SRS) and is correlated with increasing radiation to the pituitary gland. Biological effective dose (BED) is a dosimetric parameter that incorporates a time component to adjust for mechanisms of deoxyribonucleic acid repair activated during treatment. OBJECTIVE: To assess mean gland BED as a predictor of post-SRS hypopituitarism, as compared to mean gland dose, in a contemporary cohort study of patients undergoing single-fraction SRS for pituitary adenoma. METHODS: Cohort study of 97 patients undergoing single-fraction SRS from 2007 to 2014. Eligible patients had no prior pituitary irradiation, normal pre-SRS endocrine function, and >24moof endocrine follow-up. Cox proportional hazards analysiswas used to assessmean gland dose and BED as predictors of new post-SRS hypopituitarism. RESULTS: Median post-SRS follow-up was 48 mo (interquartile range [IQR], 34-68). A total of 27 patients (28%) developed new hypopituitarism at a median 22 mo (IQR, 12-36). Actuarial rates of new endocrinopathy were 17% at 2 yr (95% CI 10%-25%) and 31% at 5 yr (95% CI 20%-42%). On univariate analysis, sex (P=.02), gland volume (P=.03), mean gland dose (P <.0001), and BED significantly predicted new hypopituitarism (P <.0001). After adjusting for sex and gland volume, BED > 45 Gy(2.47) and mean gland dose > 10 Gy were significantly associated increased risk of hypopituitarism (hazard ratio [HR] = 14.32, 95% CI = 4.26-89.0, P <.0001; HR = 11.91, 95% CI = 3.54-74.0, P <.0001). CONCLUSION: BED predicted hypopituitarism more reliably than mean gland dose after pituitary adenoma SRS, but additional studies are needed to confirm these results.

Automated summary

This study found that biological effective dose (BED) is a more reliable predictor of post-SRS hypopituitarism compared to mean gland dose in patients with pituitary adenoma. Adjusted for sex and gland volume, BED > 45 Gy and mean gland dose > 10 Gy were significantly associated with an increased risk of hypopituitarism. Additional studies are needed to confirm these results.