Long-term outcomes of hypofractionated stereotactic radiotherapy for refractory functional pituitary adenoma

Refractory functional pituitary adenomas are often treated with single-session stereotactic radiosurgery (SRS) or conventionally fractionated intensity-modulated radiotherapy (IMRT). While single-fraction SRS offers convenience and short time to biochemical remission, large tumors with cranial nerve or chiasmatic involvement often preclude single-fraction SRS, and toxicity may be worse following single-fraction SRS compared with IMRT. The purpose of our study was to explore the long-term outcomes of a unique hypofractionated stereotactic radiotherapy (HSRT) regimen delivered in 2–5 fractions. After approval, we studied 16 consecutive patients treated with HSRT for refractory functional pituitary adenoma. Study endpoints included local control, biochemical control, and toxicity. Descriptive statistics summarized endpoints and clinicopathologic factors. Sixteen patients with adrenocorticotropic hormone secretion (n = 9, 56%), growth hormone secretion (n = 4, 25%), and prolactin secretion (n = 3, 19%) were studied with a median follow-up time after HSRT of 10 years (IQR 2–14 years). Patients were treated with two (n = 8), three (n = 1), or five (n = 7) fractions to median dose of 20.5 Gy (range 16–32 Gy). HSRT was well-tolerated with no acute side effects greater than CTCAE grade 1. Local control was 100%, and biochemical control at last follow-up was 58%. Over 142 years patient-years, no instances of optic neuropathy, secondary malignancy, malignant transformation, radionecrosis, cavernous sinus cranial neuropathy, or cerebrovascular complications were noted. HSRT for refractory pituitary adenoma is well-tolerated with long-term local and biochemical control comparable with single-fraction SRS or IMRT. Prospective studies should evaluate whether HSRT provides non-inferior biochemical control and improved toxicity compared with single-fraction SRS.