Introduction: Nonfunctioning pituitary macroadenomas frequently invade the cavernous sinus and many cannot be completely resected without undue risk. Gamma Knife radiosurgery (GKRS) is highly effective for treating residual and recurrent adenomas. However, there is no consensus as to whether GKRS should be used early to treat residual adenoma or after a set period of clinical observation during which adenoma growth is demonstrated. Given the high incidence of adenoma progression after subtotal resection over time, the present study examines the potential utility of GKRS performed shortly after transsphenoidal surgery versus expectant management with delayed GKRS treatment.

Methods: This is a retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1996 to 2013 at the University of Virginia. Patients were stratified based on interval between resection and radiosurgery. Operative results, imaging and clinical outcomes were compared across groups following early (<6 months) or late (>6 months) radiosurgery.

Results: Sixty-four patients met our study criteria and were grouped based on early (N=32) or late (N=32) GKRS following transsphenoidal resection. There was greater risk of adenoma progression after GKRS in the late radiosurgical group (p=0.027) over a median radiographic follow-up period of 68.5 months. Furthermore, there was a significantly higher occurrence of post-GKRS endocrinopathy in the late radiosurgical cohort (p=0.041). Seventeen percent of patients without endocrinopathy in the early cohort developed new endocrinopathies following radiosurgery versus 64% in the late cohort (p=0.036). This difference was secondary to a significantly higher rate of adenoma growth during the observation period in the late treatment cohort (p=0.014).

Conclusions: Early treatment with GKRS appears to decrease the rate of radiographic and symptomatic progression of sub-totally resected nonfunctioning pituitary macroadenomas compared to late GKRS treatment after a period of expectant management. Delaying radiosurgery may place patients at increased risk for adenoma progression and endocrinopathy.

Patient Care: Gamma knife radiosurgery is highly effective in controlling tumor growth in patients with nonfunctioning macroadenomas, however, there is a relatively high risk for developing hypopituitarism after radiosurgery. This study helps to further understand the potential role of radiosurgery following subtotal resection of nonfunctioning pituitatry macroadenomas which show a high incidence of recurrence. We may also move toward a more specific theory of the natural history of these tumors and diagnosis and assessment of therapeutic change.

Learning Objectives: 1. Participants should be able to recognize the role for adjuvant radiosurgery following transsphenoidal resection of nonfunctioning pituitary macroadenomas 2. Participants should learn the risks and benefits of subtotal resection of tumors invading cavernous sinus with high rates of recurrence 3. Participants should gain insight into the clinical course of operative patients with nonfunctioning pituitary macroadenomas

References: Dallapiazza RF, Grober Y, Starke RM, Laws ER, Jane JA. Long-term Results of Endonasal Endoscopic Transsphenoidal Resection of Nonfunctioning Pituitary Macroadenomas. Neurosurgery. 2014. Sheehan JP, Kondziolka D, Flickinger J, Lunsford LD. Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma. J Neurosurg. 2002;97(5 Suppl):408-14. Sheehan JP, Kondziolka D, Flickinger J, Lunsford LD. Radiosurgery for nonfunctioning pituitary adenoma. Neurosurg Focus. 2003;14(5):e9. Sheehan JP, Starke RM, Mathieu D, et al. Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: a multicenter study. J Neurosurg. 2013;119(2):446-56. Starke RM, Williams BJ, Jane JA, Sheehan JP. Gamma Knife surgery for patients with nonfunctioning pituitary macroadenomas: predictors of tumor control, neurological deficits, and hypopituitarism. J Neurosurg. 2012;117(1):129-35.