Early versus late Gamma Knife radiosurgery following transsphenoidal surgery for nonfunctioning pituitary macroadenomas: a multicenter matched-cohort study

Abstract

OBJECTIVE Gamma Knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of imaging-defined progression of tumor. Given the high incidence of adenoma progression after subtotal resection over time, the present study intended to evaluate the effect of timing of radiosurgery on outcome. METHODS This is a multicenter retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions affiliated with the International Gamma Knife Research Foundation. Patients were matched by adenoma and radiosurgical parameters and stratified based on the interval between last resection and radiosurgery. Operative results, imaging data, and clinical outcomes were compared across groups following early (≤ 6 months after resection) or late (> 6 months after resection) radiosurgery. RESULTS After matching, 222 patients met the authors' study criteria (from an initial collection of 496 patients) and were grouped based on early (n = 111) or late (n = 111) GKRS following transsphenoidal surgery. There was a greater risk of tumor progression after GKRS (p = 0.013) and residual tumor (p = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. No significant difference in the occurrence of post-GKRS endocrinopathy was observed (p = 0.68). Thirty percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 27% in the late cohort (p = 0.84). Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after original presentation (p = 0.32). CONCLUSIONS In this study, early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late radiosurgery. Delaying radiosurgery may increase patient risk for long-term adenoma progression. The timing of radiosurgery does not appear to significantly affect the rate of delayed endocrinopathy.

Deferred Radiotherapy After Debulking of Non-functioning Pituitary Macroadenomas: Clinical Outcomes

“…Additionally, there was the intriguing finding of an increased risk of endocrinopathy in general, and new endocrinopathy for the group receiving delayed therapy, which was attributed to tumor growth. A multi institutional follow up (22) from the same group showed new endocrinopathy rates of 11.8% in the early GK-SRS group, and 9% in the late GK-SRS group, for a combined rate of 21% over the 6 year follow up. We report a new endocrinopathy rate of 20% with a median follow up of 10 years.…”

Use of radiotherapy after pituitary surgery for non-functioning pituitary adenomas

“…Several retrospective series did not show differences in terms of tumor control and toxicity between patients receiving immediate postoperative FCRT compared to those treated at the time of recurrence or progression (58,61). By contrast, series reporting clinical outcomes after SRS suggest that early postoperative treatment may provide the best therapeutic option for patients with residual tumor, preventing the development of neurological deficits associated with tumor growth and reducing the risk of long-term toxicity (42,94).…”

Growth of Pituitary Macroadenomas Postpartial Resection: Implications for Adjuvant Radiotherapy

“…Recently, Pomeraniec et al performed a matched-cohort comparison on the timing of stereotactic radiosurgery (earlier vs. later treatment) in patients with subtotally resected adenomas. 11 The authors concluded that earlier treatment was associated with a lower risk of radiological progression compared with expectant management followed by late radiosurgery. Whether a threshold volume of 3.95 mL is the optimal volume remains to be confirmed, particularly considering that our analysis was done using a continuous variable in a relative small number of patients.…”