Role of biological effective dose for prediction of endocrine remission in acromegaly patients treated with stereotactic radiosurgery

Abstract

Purpose: Stereotactic radiosurgery (SRS) can be used in acromegaly patients to achieve endocrine remission. In this study we evaluate the biological effective dose (BED) as a predictor of SRS outcomes for acromegaly.

Method: This retrospective, single-center study included patients treated with single-fraction SRS with growth hormone secreting pituitary adenomas and available endocrine follow-up. Kaplan-Meier analysis was used to study endocrine remission, new pituitary deficit, and tumor control. Cox analyses were performed using two models [margin dose (model 2) versus BED (model 1)].

Results: Sixty-seven patients (53.7% male) with a median age of 46.8 years (IQR 21.2) were treated using a median dose of 25 Gy (IQR 5), and a median BED of 171.9Gy_2.47 (IQR 66.0). Five (7.5%) were treated without stopping antisecretory medication. The cumulative probability of maintained endocrine remission off suppressive medications was 62.5% [47.9-73.0] at 3 years and 76.5% [61.0-85.9] at 5 years. IGF1_i > 1.5 was a predictor of treatment failure [Hazard ratio (HR) 0.40 (0.21-0.79) in model 1, p = 0.00783]. Margin dose > 22 Gy [HR 2.33 (1.06-5.13), p = 0.03593] or a BED > 170Gy2.47 [HR 2.02 (1.06-3.86), p = 0.03370] were associated with endocrine remission. The cumulative probability of new hypopituitarism after SRS was 36.8% (CI 95% 22.4-45.9) at 3 years and 53.2% (CI 95% 35.6-66) at 5 years. BED or margin dose were not associated with new hypopituitarism.

Conclusion: BED is a strong predictor of endocrine remission in patients treated with SRS. Dose planning and optimization of the BED to > 170Gy_2.47 give a greater probability of endocrine remission in acromegalic patients.

Keywords: Acromegaly; Biological effective dose; Gamma-knife; IGF1index; Stereotactic radiosurgery.