Radiotherapy for pituitary adenomas: long-term outcome and complications

Abstract

PurposeTo evaluate long-term local control rate and toxicity in patients treated with external beam radiotherapy (EBRT) for pituitary adenomas.Materials and MethodsWe retrospectively reviewed the medical records of 60 patients treated with EBRT for pituitary adenoma at Korea University Medical Center from 1996 and 2006. Thirty-five patients had hormone secreting tumors, 25 patients had non-secreting tumors. Fifty-seven patients had received postoperative radiotherapy (RT), and 3 had received RT alone. Median total dose was 54 Gy (range, 36 to 61.2 Gy). The definition of tumor progression were as follows: evidence of tumor progression on computed tomography or magnetic resonance imaging, worsening of clinical sign requiring additional operation or others, rising serum hormone level against a previously stable or falling value, and failure of controlling serum hormone level so that the hormone level had been far from optimal range until last follow-up. Age, sex, hormone secretion, tumor extension, tumor size, and radiation dose were analyzed for prognostic significance in tumor control.ResultsMedian follow-up was 5.7 years (range, 2 to 14.4 years). The 10-year actuarial local control rates for non-secreting and secreting adenomas were 96% and 66%, respectively. In univariate analysis, hormone secretion was significant prognostic factor (p = 0.042) and cavernous sinus extension was marginally significant factor (p = 0.054) for adverse local control. All other factors were not significant. In multivariate analysis, hormone secretion and gender were significant. Fifty-three patients had mass-effect symptoms (headache, dizziness, visual disturbance, hypopituitarism, loss of consciousness, and cranial nerve palsy). A total of 17 of 23 patients with headache and 27 of 34 patients with visual impairment were improved. Twenty-seven patients experienced symptoms of endocrine hypersecretion (galactorrhea, amenorrhea, irregular menstruation, decreased libido, gynecomastia, acromegaly, and Cushing's disease). Amenorrhea was abated in 7 of 10 patients, galactorrhea in 8 of 8 patients, acromegaly in 7 of 11 patients, Cushing's disease in 4 of 4 patients. Long-term complication was observed in 4 patients; 3 patients with cerebrovascular accident, 1 patient developed dementia. Of these patients, 3 of 4 received more than 60 Gy of irradiation.ConclusionEBRT is highly effective in preventing recurrence and reducing mass effect of non-secreting adenoma. Effort to improve tumor control of secreting adenoma is required. Careful long-term follow-up is required when relatively high dose is applied. Modern radiosurgery or proton RT may be options to decrease late complications.

Excess Mortality Associated With Hypopituitarism in Adults: A Meta-Analysis of Observational Studies

“…Increased risk of atherosclerosis and strokes had been demonstrated in patients who had cranial irradiation for other reasons (25,26). Patients treated with irradiation for pituitary adenomas had strokes near radiation field (27). The vasculopathy related to pituitary irradiation, and the metabolic syndrome and higher prevalence of atherosclerosis related to pituitary insufficiency, are all factors contributing to excess cerebrovascular mortality in hypopituitary adults.…”

Post-surgical management of non-functioning pituitary adenoma

“…Vascular risk is elevated in female subjects and in case of pituitary surgery preceding RT [81]. Stroke has also been associated with classical external ("conventional") RT [73,79,81,82]. The specific technique may be implicated, notably the use of two lateral beams, margin width, and use of 2D dosimetry.…”

Radiation-induced hypopituitarism

“…In those patients, multiple pituitary hormone deficiencies evolve frequently following conventional irradiation schedules with doses that, otherwise, mostly result in isolated GH deficiency [2,3,42,43] (Table 1 and Fig. 1).…”