How can fractionated radiotherapy and stereotactic radiosurgery be used for pituitary adenomas?

BACKGROUND Pituitary adenomas are relatively common, accounting for 10-20% of primary central nervous system tumors. For nonsecretory adenomas, control of tumor growth and retention of vision are the most important objectives, whereas for hormone-secretory adenomas correction of endocrinopathies becomes a priority. Radiotherapy is indicated for patients whose tumors do not respond to surgery or medical therapies. OBJECTIVE The aim of the study was to determine the efficacy and safety of fractionated radiotherapy (FRT) and that of stereotactic radiosurgery (SRS) for the treatment of patients with pituitary adenomas. DESIGN AND INTERVENTION Patients with pituitary adenomas in whom surgical and medical treatment had failed to eradicate the tumor or normalize hormone secretion, or in whom surgery was not appropriate for medical reasons, were included in this retrospective cohort. A total of 125 consecutive patients were treated with FRT or underwent SRS between January 1995 and April 2006 - a mean total dose of 50.4Gy (range 48-54Gy) was administered as FRT in 64 patients and, following installation of the gamma-knife radiosurgery device in 2002, 61 patients underwent SRS with the gamma-knife technique at a mean marginal dose of 25.1Gy (range 9-30Gy). Inclusion criteria for SRS were maximum tumor diameter of 30 mm, and distance >= 2mrn between the tumor and the optic chiasm. FRT was provided if tumors were located close to the optic apparatus, regardless of tumor size. OUTCOME MEASURES End points included the time to tumor progression and endocrine outcomes. RESULTS Patients with pituitary adenomas (54 hormone-secreting and 71 nonfunctioning) were followed up for a mean of 36.8 months (range 2-140 months); 4 (3.2%) had tumor progression (an increase in tumor volume). For the whole group at 2 years and 4 years, rates of progression-free survival were 99% and 97%, respectively, and objective response rates were 39.5% and 81.8%, respectively. There was no observable difference in tumor growth control between the FRT and SRS groups. For those patients with secretory adenomas, receiving either FRT or SRS, the complete remission rates for endocrinologic parameters were 26.2% at 2 years and 76.3% at 4 years. Complete remission was attained in 14 (43.8%) patients in the SRS group and in 8 (36.4%) patients in the FRT group. Median values for time to complete remission were 26 months in the SRS group and 63 months in the FRT group (P = 0.0068). According to multivariate analysis, the use of SRS versus FRT (P=0.23) and the type of secretory adenoma (corticotropin-secreting versus growth-hormone-secreting or prolactin-secreting; P=0.005) were statistically significantly correlated with outcome. Hypopituitarism that required hormone replacement therapy developed as a delayed complication in 11 of 95 (11.6%) patients at a median of 84 months from radiotherapy. CONCLUSION Single-dose radiosurgery produces a more prompt effect than FRT on the hypersecretion of pituitary hormones and can be recommended over FRT in some patients.