Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas
Authors: Shaaban Ahmed , Dumot Chloé , Mantziaris Georgios , Dayawansa Sam , Peker Selcuk , Samanci Yavuz , Nabeel Ahmed M. , Reda Wael A. , Tawadros Sameh R. , Abdel Karim Khaled , El-Shehaby Amr M. N. , Emad Eldin Reem M. , Ragab Abdelsalam Ahmed , Liscak Roman , May Jaromir , Mashiach Elad , De Nigris Vasconcellos Fernando , Bernstein Kenneth , Kondziolka Douglas , Speckter Herwin , Mota Ruben , Brito Anderson , Bindal Shray K. , Niranjan Ajay , Lunsford L. Dade , Benjamin Carolina Gesteira , Almeida Timoteo , Mao Jennifer Z. , Mathieu David , Tourigny Jean-Nicolas , Tripathi Manjul , Palmer Joshua David , Matsui Jennifer , Crooks Joseph , Wegner Rodney E. , Shepard Matthew J. , Sheehan Jason P. 
Published: March 2024

OBJECTIVE
Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS.

METHODS
This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology.

RESULTS
There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9–61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43–61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7–10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%–95%), 87% (95% CI 83%–91%), 86% (95% CI 82%–90%), and 69% (95% CI 59%–81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9–10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%–87%), 81% (95% CI 77%–85%), 78% (95% CI 74%–83%), and 71% (95% CI 63%–79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7–0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7–0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09–1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group.

CONCLUSIONS
SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.